Taisuke Mori - Academia.edu (original) (raw)
Papers by Taisuke Mori
Scientific Reports
The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is incre... more The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center’s experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL...
The Laryngoscope, 2014
Treatment of head and neck squamous cell carcinoma (HNSCC) often requires radiotherapy, but relap... more Treatment of head and neck squamous cell carcinoma (HNSCC) often requires radiotherapy, but relapse can occur. There is, therefore, an urgent need for the identification of a predictive novel biomarker for radiosensitivity. The epithelial cell adhesion molecule (EpCAM) has been shown to promote the transformation of malignant tumors, and EpCAM may have prognostic significance, but it is not known if EpCAM determines prognosis, especially with respect to radiotherapy. Therefore, we determined the incidence of the expression of EpCAM in HNSCC and analyzed the prognostic value in patients with early-stage glottic cancer treated with radiotherapy. Retrospective analysis. All patients with HNSCCs examined in our hospital between January 2012 and February 2013 were analyzed prospectively for the expression of EpCAM. T1-2N0 glottic cancer patients who were primarily treated by radiation therapy between 1995 and 2008 were retrospectively investigated. Patients with or without local recurren...
Japanese Journal of Oral & Maxillofacial Surgery, 1998
American Journal of Surgical Pathology
BMC Cancer
Background: Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodul... more Background: Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodules; however, some features such as atypia of undetermined significance or follicular lesion of undetermined significance can confound efforts to identify malignancies. Similar to BRAF, cyclin D1 may be a strong marker of cell proliferation. Methods: One hundred two patients with thyroidal nodule were enrolled in this prospective study. Expression of cyclin D1 in thyroid nodules was determined by immunohistochemistry using both surgical specimens and their cytological specimens. The identification of the optimal cut off points for the diagnosis of malignancy were evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) of markers were evaluated from crosstabs based on cut off points and significance were calculated. We also analyzed genetic variants by target NGS for thyroid nodule samples. Results: The positive predictive value (PPV) and median stain ratio (MSR) of cyclin D1 nuclear staining was determined in papillary thyroid carcinoma (PPV = 91.5%, MSR = 48.5%), follicular adenoma (PPV = 66.7%, MSR = 13. 1%), and adenomatous goiter and inflammation controls (MSR = 3.4%). In FNA samples, a threshold of 46% of immunolabelled cells allows to discriminate malignant lesions from benign ones (P < 0.0001), with 81% sensitivity and 100% specificity. A 46% cutoff value for positive cyclin D1 immunostaining in thyroid cells demonstrated 81% sensitivity and 100% specificity. In surgical specimens, ROC curve analysis showed a 5.8% cyclin D1 immunostaining score predicted thyroid neoplasms at 94.4% sensitivity and 92.3% specificity (P = 0.003), while a 15.7% score predicted malignancy at 86.4% sensitivity and 80.5% specificity (P < 0.0001). Finally, three tested clinico-pathological variables (extra thyroidal extension, intraglandular metastasis, and lymph node metastasis) were significant predictors of cyclin D1 immunostaining (P < 0.001). Conclusion: Our cytological cyclin D1 screening system provides a simple, accurate, and convenient diagnostic method in precision medicine enabling ready determination of personalized treatment strategies for patients by next generation sequencing using cytological sample.
JOURNAL OF JAPAN SOCIETY FOR HEAD AND NECK SURGERY
Journal of Clinical Investigation
Poroma is a benign skin tumor exhibiting terminal sweat gland duct differentiation. The present s... more Poroma is a benign skin tumor exhibiting terminal sweat gland duct differentiation. The present study aimed to explore the potential role of gene fusions in the tumorigenesis of poromas. RNA sequencing and reverse transcription PCR identified highly recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poromas (92/104 lesions, 88.5%) and their rare malignant counterpart, porocarcinomas (7/11 lesions, 63.6%). A WWTR1-NUTM1 fusion was identified in a single lesion of poroma. Fluorescent in-situ hybridization confirmed genomic rearrangements involving these genetic loci. Immunohistochemical staining could readily identify the YAP1 fusion products as nuclear expression of the N-terminal portion of YAP1 with a lack of the C-terminal portion. YAP1 and WWTR1, also known as YAP and TAZ, respectively, encode paralogous transcriptional activators of TEAD, which are negatively regulated by the Hippo signaling pathway. The YAP1 and WWTR1 fusions strongly transactivated a TEAD reporter and promoted anchorage-independent growth, confirming their tumorigenic roles. Our results demonstrate the frequent presence of transforming YAP1 fusions in poromas and porocarcinomas and suggest YAP1/TEAD-dependent transcription as a candidate therapeutic target against porocarcinoma.
Journal of Neurological Surgery Part B: Skull Base
Objective This study aimed to determine the adequate resection margin in skull base surgery for h... more Objective This study aimed to determine the adequate resection margin in skull base surgery for head and neck sarcoma. Design We retrospectively reviewed 22 sarcomas with skull base invasion. Induction chemotherapy, followed by surgery and postoperative radiotherapy and adjuvant chemotherapy, was performed in 18 patients with chemosensitive sarcomas, and surgery with or without postoperative radiotherapy was performed in four patients with chemoresistant sarcomas. Radical resection was performed in patients with chemosensitive sarcomas with a poor response to induction chemotherapy and in patients with chemoresistant sarcomas. Conservative resection with close surgical margin was performed in patients with chemosensitive sarcomas with a good response to induction chemotherapy. Setting and Participants This single-centered retrospective study included patients from the National Cancer Center Hospital, Japan. Results The response to induction chemotherapy was significantly associated ...
Scientific Reports
Fluorescence visualization devices (FVs) are useful for detecting malignant lesions because of th... more Fluorescence visualization devices (FVs) are useful for detecting malignant lesions because of their simple and noninvasive application. However, their quantitative application has been challenging. This study aimed to quantitatively and statistically evaluate the change in fluorescence intensity (FI) during the progression from normal epithelium to squamous cell carcinoma using a reproducible animal tongue carcinogenesis model. To establish this model, rats were treated with 50 ppm 4-Nitroquinoline 1-oxide (4NQO) in their drinking water for 10, 15, and 20 weeks. After 4NQO administration, each rat tongue was evaluated by gross observation, histology, and FI measurements. Fluorescence images were captured by FV, and ImageJ was used to measure FI, which was analyzed quantitatively and statistically. The establishment of a reproducible tumor progression model was confirmed, showing precancerous lesions (low-grade dysplasia [LGD]), early cancers (high-grade dysplasia/carcinoma in situ [HGD/CIS]), and advanced cancers (Cancer). This carcinogenesis model was quantitatively evaluated by FI. The FI of LGD stage was 54.6, which was highest intensity of all groups. Subsequently, the HGD/ CIS and Cancer stages showed decreased FI (HGD/CIS: 46.1, Cancer: 49.1) and manifested as dark spots. This result indicates that FI had more variation and a wider range with increasing tumor progression. We demonstrated that FI migration and an uneven distribution are consistent with tumor progression. Since each step of tumor progression occurs reproducibly in this animal model, statistical evaluation was possible. In addition, tumor progression can be monitored by this new FI analysis method in humans. The morbidity of oral cancer has increased over the past few decades. While treatment methods are improving, survival rates remain low, largely because it is hard to distinguish oral mucosal lesions, such as oral potentially malignant disorders (OPMDs), from early stage cancer. Although the oral cavity can be diagnosed via direct viewing, the early detection of oral premalignant or cancerous lesions remains difficult 1. The grade of dysplasia is not easy to differentiate by general pathologists. If these lesions have to be monitored over time, the use of non-invasive methods rather than repeated biopsies will benefit patients. Therefore, noninvasive methods are preferable for diagnosing these lesions at an early stage. Recently, it has been demonstrated that fluorescence visualization devices (FVs) are useful for detecting lesions of the oral mucosa, and especially to discriminate between OPMDs such as oral lichen planus, leukoplakia, and dysplasia 2-6. Among its benefits, the FV system is simple and noninvasive to use 7,8. The IllumiScan ® FV (Shofu Inc, Kyoto, Japan) uses 425 nm wavelength visual light to distinguish between normal and abnormal mucosa 9-11. Normal oral mucosa has a fluorescence spectral range of approximately 375 nm to 440 nm. Under this light, normal mucosa emits pale green fluorescence while abnormal areas absorb the fluorescent light, resulting in dark patches with fluorescence visualization loss (FVL) 12,13. However, it has not yet been determined why abnormal parts of the mucosa cause FVL. It has been shown that FV can detect differences in fluorescence between normal mucosa and epithelial dysplasia 1,3,14. Other reports have demonstrated that FV can be used as a diagnostic tool of for oral malignant disorders, but such observations have not been evaluated quantitatively 15. This lack of quantification may be a result of human oral cancer being caused by many factors, including smoking, alcohol consumption, and viral infection. Moreover, different parts of the oral cavity mucosa vary in the degree
Annals of Surgical Oncology
Annals of Surgical Oncology
Background. This study elucidates the clinical impact of surgical treatment of head and neck squa... more Background. This study elucidates the clinical impact of surgical treatment of head and neck squamous cell carcinoma (HNSCC) based on a detailed search of all exons of the TP53 gene and p53 protein phenotypic analysis using formalin-fixed paraffin-embedded (FFPE) specimens. Methods. Clinically well-annotated FFPE specimens from 317 patients with HNSCC treated by surgery were examined by all-exon TP53 sequencing using a next-generation sequencer and p53 protein phenotype by immunohistochemistry. After excluding human papillomavirusassociated oropharyngeal carcinomas, two risk categories were classified as ''p53 adverse function'' and ''p53 favorable function'' based on TP53 mutation status and p53 protein phenotype. Mutation in PIK3CA, AKT, and HRAS was also evaluated by target sequence. Cox proportional hazards regression models were used for statistical analysis of clinical outcomes. Receiver operating characteristic curve analysis was used to determine the optimal surgical margin cutoff for local recurrence. Local control rates were compared between the risk groups using Fisher's exact test. Results. Multivariate analysis identified ''p53 adverse function'' as an independent poor predictor of overall survival, local control, and distant metastasis-free survival. In oral cavity cancer, the optimal surgical margin cutoff associated with local recurrence was 6 mm. In patients with surgical margin [ 6 mm, the ''p53 adverse function'' group demonstrated significantly higher local recurrence rate than the ''p53 favorable function'' group. PIK3CA, AKT, or HRAS mutation did not correlate with improved overall survival. Conclusions. All-exon TP53 sequencing and p53 protein phenotype analysis using FFPE specimens can accurately predict clinical outcomes.
Blood
Key Points Platelets were manufactured on a large scale from a novel human ASCL as a donor-indepe... more Key Points Platelets were manufactured on a large scale from a novel human ASCL as a donor-independent source. ASCL-PLTs have similar characteristics to those of peripheral platelets and might have an additional function as mesenchymal-like cells.
Investigative ophthalmology & visual science, Oct 1, 2017
Adenocarcinomas or adenomas derived from pigmented ciliary epithelium (APCE) are exceptionally ra... more Adenocarcinomas or adenomas derived from pigmented ciliary epithelium (APCE) are exceptionally rare ocular tumors. These tumors have pigmented and epithelioid features, and some APCEs are negative for keratin markers and positive for melanocytic markers. It is especially difficult to distinguish APCEs from uveal melanoma (UM). Accordingly, we examined protein expression and genetic mutations associated with APCE to facilitate diagnosis. Five APCE and 11 UM samples were obtained from patients during surgical resection at our institute. APCE and UM ocular structures were compared comprehensively. Protein expression and genetic alterations involved in malignant melanoma were evaluated. SOX10 was expressed diffusely in all 11 UMs and in surrounding uveal or choroidal melanocytes, but not in the APCEs or nontumorous pigmented epithelia. Additionally, the expression patterns of cytokeratins and melanocytic markers differed between UMs and APCEs. We identified BRAF V600E mutations in four ...
Pathology, research and practice, May 1, 2018
Histopathology, Jan 19, 2018
Ewing sarcoma is a small round cell tumour that affects bone and soft tissues. Although the detec... more Ewing sarcoma is a small round cell tumour that affects bone and soft tissues. Although the detection of the specific fusion gene is a robust method of its diagnosis, immunohistochemistry may serve as a practical surrogate. Recent tissue microarray studies suggested that PAX7 is a novel marker, because it was expressed consistently in Ewing sarcoma, in addition to rhabdomyosarcoma and synovial sarcoma. Here, we evaluated the utility of PAX7 immunohistochemistry in whole-tissue sections of an expanded array of round cell malignancies with adequate molecular characterisation. We stained 30 molecularly confirmed Ewing sarcomas, one EWSR1-NFATC2 sarcoma and 141 non-Ewing round cell tumours by a monoclonal antibody against PAX7. Staining was considered positive if at least 5% of tumour cells were stained. PAX7 was expressed in 27 of 30 Ewing sarcomas (90%), mainly in a diffuse and strong manner. Although NKX2-2 showed similar sensitivity, PAX7 showed more extensive and strong reactivity....
Histopathology, Jan 19, 2018
Sessile serrated adenoma/polyp (SSA/P) is regarded as a genetically homogeneous entity, with most... more Sessile serrated adenoma/polyp (SSA/P) is regarded as a genetically homogeneous entity, with most lesions harbouring the BRAF V600E mutation. The present study aimed to reappraise the genetic heterogeneity of SSA/Ps and its clinicopathological significance. We performed next-generation sequencing of 272 SSA/Ps without dysplasia and evaluated morphological and molecular features associated with the respective genotypes. BRAF V600E, BRAF non-V600E, KRAS and NRAS mutations were found in 223 (82.0%), three (1.2%), 28 (10.3%) and one lesion (0.4%), respectively. Notably, all lesions with BRAF non-V600E mutations had either KRAS or NRAS mutations concurrently. Twenty SSA/Ps (7.4%) were negative for these mutations. KRAS-mutated SSA/Ps were located more often in the distal colon (42%) compared to those with the BRAF V600E mutation (14%). Histologically, minimally serrated crypts and goblet cell-rich crypts were more common in KRAS-mutated and mutation-negative SSA/Ps. However, in most inst...
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, Jan 22, 2018
We describe a series of colorectal polyps characterized by mixed adenomatous and serrated feature... more We describe a series of colorectal polyps characterized by mixed adenomatous and serrated features, herein referred to as superficially serrated adenomas. Twenty superficially serrated adenomas were obtained from 11 female and 9 male patients aged 62-87 years. Most lesions endoscopically appeared as small sessile polyps, but larger lesions were plaque-like (2-20 mm; median, 5 mm). Eighteen lesions (90%) were located in the sigmoid colon or rectum. They consisted primarily of straight, adenomatous glands but showed serration confined to the superficial layer. Immunohistochemistry revealed CK20 expression in the upper layer. Proliferating cells, determined by their expression of Ki-67, were localized to the middle to bottom layers. Genetic analyses identified KRAS mutations in 19 lesions and a BRAF mutation in one lesion. Furthermore, RSPO fusions and/or overexpression were observed in 18 lesions and truncating APC mutations were observed in the two remaining lesions. Consistent with ...
Scientific Reports
The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is incre... more The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center’s experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL...
The Laryngoscope, 2014
Treatment of head and neck squamous cell carcinoma (HNSCC) often requires radiotherapy, but relap... more Treatment of head and neck squamous cell carcinoma (HNSCC) often requires radiotherapy, but relapse can occur. There is, therefore, an urgent need for the identification of a predictive novel biomarker for radiosensitivity. The epithelial cell adhesion molecule (EpCAM) has been shown to promote the transformation of malignant tumors, and EpCAM may have prognostic significance, but it is not known if EpCAM determines prognosis, especially with respect to radiotherapy. Therefore, we determined the incidence of the expression of EpCAM in HNSCC and analyzed the prognostic value in patients with early-stage glottic cancer treated with radiotherapy. Retrospective analysis. All patients with HNSCCs examined in our hospital between January 2012 and February 2013 were analyzed prospectively for the expression of EpCAM. T1-2N0 glottic cancer patients who were primarily treated by radiation therapy between 1995 and 2008 were retrospectively investigated. Patients with or without local recurren...
Japanese Journal of Oral & Maxillofacial Surgery, 1998
American Journal of Surgical Pathology
BMC Cancer
Background: Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodul... more Background: Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodules; however, some features such as atypia of undetermined significance or follicular lesion of undetermined significance can confound efforts to identify malignancies. Similar to BRAF, cyclin D1 may be a strong marker of cell proliferation. Methods: One hundred two patients with thyroidal nodule were enrolled in this prospective study. Expression of cyclin D1 in thyroid nodules was determined by immunohistochemistry using both surgical specimens and their cytological specimens. The identification of the optimal cut off points for the diagnosis of malignancy were evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) of markers were evaluated from crosstabs based on cut off points and significance were calculated. We also analyzed genetic variants by target NGS for thyroid nodule samples. Results: The positive predictive value (PPV) and median stain ratio (MSR) of cyclin D1 nuclear staining was determined in papillary thyroid carcinoma (PPV = 91.5%, MSR = 48.5%), follicular adenoma (PPV = 66.7%, MSR = 13. 1%), and adenomatous goiter and inflammation controls (MSR = 3.4%). In FNA samples, a threshold of 46% of immunolabelled cells allows to discriminate malignant lesions from benign ones (P < 0.0001), with 81% sensitivity and 100% specificity. A 46% cutoff value for positive cyclin D1 immunostaining in thyroid cells demonstrated 81% sensitivity and 100% specificity. In surgical specimens, ROC curve analysis showed a 5.8% cyclin D1 immunostaining score predicted thyroid neoplasms at 94.4% sensitivity and 92.3% specificity (P = 0.003), while a 15.7% score predicted malignancy at 86.4% sensitivity and 80.5% specificity (P < 0.0001). Finally, three tested clinico-pathological variables (extra thyroidal extension, intraglandular metastasis, and lymph node metastasis) were significant predictors of cyclin D1 immunostaining (P < 0.001). Conclusion: Our cytological cyclin D1 screening system provides a simple, accurate, and convenient diagnostic method in precision medicine enabling ready determination of personalized treatment strategies for patients by next generation sequencing using cytological sample.
JOURNAL OF JAPAN SOCIETY FOR HEAD AND NECK SURGERY
Journal of Clinical Investigation
Poroma is a benign skin tumor exhibiting terminal sweat gland duct differentiation. The present s... more Poroma is a benign skin tumor exhibiting terminal sweat gland duct differentiation. The present study aimed to explore the potential role of gene fusions in the tumorigenesis of poromas. RNA sequencing and reverse transcription PCR identified highly recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poromas (92/104 lesions, 88.5%) and their rare malignant counterpart, porocarcinomas (7/11 lesions, 63.6%). A WWTR1-NUTM1 fusion was identified in a single lesion of poroma. Fluorescent in-situ hybridization confirmed genomic rearrangements involving these genetic loci. Immunohistochemical staining could readily identify the YAP1 fusion products as nuclear expression of the N-terminal portion of YAP1 with a lack of the C-terminal portion. YAP1 and WWTR1, also known as YAP and TAZ, respectively, encode paralogous transcriptional activators of TEAD, which are negatively regulated by the Hippo signaling pathway. The YAP1 and WWTR1 fusions strongly transactivated a TEAD reporter and promoted anchorage-independent growth, confirming their tumorigenic roles. Our results demonstrate the frequent presence of transforming YAP1 fusions in poromas and porocarcinomas and suggest YAP1/TEAD-dependent transcription as a candidate therapeutic target against porocarcinoma.
Journal of Neurological Surgery Part B: Skull Base
Objective This study aimed to determine the adequate resection margin in skull base surgery for h... more Objective This study aimed to determine the adequate resection margin in skull base surgery for head and neck sarcoma. Design We retrospectively reviewed 22 sarcomas with skull base invasion. Induction chemotherapy, followed by surgery and postoperative radiotherapy and adjuvant chemotherapy, was performed in 18 patients with chemosensitive sarcomas, and surgery with or without postoperative radiotherapy was performed in four patients with chemoresistant sarcomas. Radical resection was performed in patients with chemosensitive sarcomas with a poor response to induction chemotherapy and in patients with chemoresistant sarcomas. Conservative resection with close surgical margin was performed in patients with chemosensitive sarcomas with a good response to induction chemotherapy. Setting and Participants This single-centered retrospective study included patients from the National Cancer Center Hospital, Japan. Results The response to induction chemotherapy was significantly associated ...
Scientific Reports
Fluorescence visualization devices (FVs) are useful for detecting malignant lesions because of th... more Fluorescence visualization devices (FVs) are useful for detecting malignant lesions because of their simple and noninvasive application. However, their quantitative application has been challenging. This study aimed to quantitatively and statistically evaluate the change in fluorescence intensity (FI) during the progression from normal epithelium to squamous cell carcinoma using a reproducible animal tongue carcinogenesis model. To establish this model, rats were treated with 50 ppm 4-Nitroquinoline 1-oxide (4NQO) in their drinking water for 10, 15, and 20 weeks. After 4NQO administration, each rat tongue was evaluated by gross observation, histology, and FI measurements. Fluorescence images were captured by FV, and ImageJ was used to measure FI, which was analyzed quantitatively and statistically. The establishment of a reproducible tumor progression model was confirmed, showing precancerous lesions (low-grade dysplasia [LGD]), early cancers (high-grade dysplasia/carcinoma in situ [HGD/CIS]), and advanced cancers (Cancer). This carcinogenesis model was quantitatively evaluated by FI. The FI of LGD stage was 54.6, which was highest intensity of all groups. Subsequently, the HGD/ CIS and Cancer stages showed decreased FI (HGD/CIS: 46.1, Cancer: 49.1) and manifested as dark spots. This result indicates that FI had more variation and a wider range with increasing tumor progression. We demonstrated that FI migration and an uneven distribution are consistent with tumor progression. Since each step of tumor progression occurs reproducibly in this animal model, statistical evaluation was possible. In addition, tumor progression can be monitored by this new FI analysis method in humans. The morbidity of oral cancer has increased over the past few decades. While treatment methods are improving, survival rates remain low, largely because it is hard to distinguish oral mucosal lesions, such as oral potentially malignant disorders (OPMDs), from early stage cancer. Although the oral cavity can be diagnosed via direct viewing, the early detection of oral premalignant or cancerous lesions remains difficult 1. The grade of dysplasia is not easy to differentiate by general pathologists. If these lesions have to be monitored over time, the use of non-invasive methods rather than repeated biopsies will benefit patients. Therefore, noninvasive methods are preferable for diagnosing these lesions at an early stage. Recently, it has been demonstrated that fluorescence visualization devices (FVs) are useful for detecting lesions of the oral mucosa, and especially to discriminate between OPMDs such as oral lichen planus, leukoplakia, and dysplasia 2-6. Among its benefits, the FV system is simple and noninvasive to use 7,8. The IllumiScan ® FV (Shofu Inc, Kyoto, Japan) uses 425 nm wavelength visual light to distinguish between normal and abnormal mucosa 9-11. Normal oral mucosa has a fluorescence spectral range of approximately 375 nm to 440 nm. Under this light, normal mucosa emits pale green fluorescence while abnormal areas absorb the fluorescent light, resulting in dark patches with fluorescence visualization loss (FVL) 12,13. However, it has not yet been determined why abnormal parts of the mucosa cause FVL. It has been shown that FV can detect differences in fluorescence between normal mucosa and epithelial dysplasia 1,3,14. Other reports have demonstrated that FV can be used as a diagnostic tool of for oral malignant disorders, but such observations have not been evaluated quantitatively 15. This lack of quantification may be a result of human oral cancer being caused by many factors, including smoking, alcohol consumption, and viral infection. Moreover, different parts of the oral cavity mucosa vary in the degree
Annals of Surgical Oncology
Annals of Surgical Oncology
Background. This study elucidates the clinical impact of surgical treatment of head and neck squa... more Background. This study elucidates the clinical impact of surgical treatment of head and neck squamous cell carcinoma (HNSCC) based on a detailed search of all exons of the TP53 gene and p53 protein phenotypic analysis using formalin-fixed paraffin-embedded (FFPE) specimens. Methods. Clinically well-annotated FFPE specimens from 317 patients with HNSCC treated by surgery were examined by all-exon TP53 sequencing using a next-generation sequencer and p53 protein phenotype by immunohistochemistry. After excluding human papillomavirusassociated oropharyngeal carcinomas, two risk categories were classified as ''p53 adverse function'' and ''p53 favorable function'' based on TP53 mutation status and p53 protein phenotype. Mutation in PIK3CA, AKT, and HRAS was also evaluated by target sequence. Cox proportional hazards regression models were used for statistical analysis of clinical outcomes. Receiver operating characteristic curve analysis was used to determine the optimal surgical margin cutoff for local recurrence. Local control rates were compared between the risk groups using Fisher's exact test. Results. Multivariate analysis identified ''p53 adverse function'' as an independent poor predictor of overall survival, local control, and distant metastasis-free survival. In oral cavity cancer, the optimal surgical margin cutoff associated with local recurrence was 6 mm. In patients with surgical margin [ 6 mm, the ''p53 adverse function'' group demonstrated significantly higher local recurrence rate than the ''p53 favorable function'' group. PIK3CA, AKT, or HRAS mutation did not correlate with improved overall survival. Conclusions. All-exon TP53 sequencing and p53 protein phenotype analysis using FFPE specimens can accurately predict clinical outcomes.
Blood
Key Points Platelets were manufactured on a large scale from a novel human ASCL as a donor-indepe... more Key Points Platelets were manufactured on a large scale from a novel human ASCL as a donor-independent source. ASCL-PLTs have similar characteristics to those of peripheral platelets and might have an additional function as mesenchymal-like cells.
Investigative ophthalmology & visual science, Oct 1, 2017
Adenocarcinomas or adenomas derived from pigmented ciliary epithelium (APCE) are exceptionally ra... more Adenocarcinomas or adenomas derived from pigmented ciliary epithelium (APCE) are exceptionally rare ocular tumors. These tumors have pigmented and epithelioid features, and some APCEs are negative for keratin markers and positive for melanocytic markers. It is especially difficult to distinguish APCEs from uveal melanoma (UM). Accordingly, we examined protein expression and genetic mutations associated with APCE to facilitate diagnosis. Five APCE and 11 UM samples were obtained from patients during surgical resection at our institute. APCE and UM ocular structures were compared comprehensively. Protein expression and genetic alterations involved in malignant melanoma were evaluated. SOX10 was expressed diffusely in all 11 UMs and in surrounding uveal or choroidal melanocytes, but not in the APCEs or nontumorous pigmented epithelia. Additionally, the expression patterns of cytokeratins and melanocytic markers differed between UMs and APCEs. We identified BRAF V600E mutations in four ...
Pathology, research and practice, May 1, 2018
Histopathology, Jan 19, 2018
Ewing sarcoma is a small round cell tumour that affects bone and soft tissues. Although the detec... more Ewing sarcoma is a small round cell tumour that affects bone and soft tissues. Although the detection of the specific fusion gene is a robust method of its diagnosis, immunohistochemistry may serve as a practical surrogate. Recent tissue microarray studies suggested that PAX7 is a novel marker, because it was expressed consistently in Ewing sarcoma, in addition to rhabdomyosarcoma and synovial sarcoma. Here, we evaluated the utility of PAX7 immunohistochemistry in whole-tissue sections of an expanded array of round cell malignancies with adequate molecular characterisation. We stained 30 molecularly confirmed Ewing sarcomas, one EWSR1-NFATC2 sarcoma and 141 non-Ewing round cell tumours by a monoclonal antibody against PAX7. Staining was considered positive if at least 5% of tumour cells were stained. PAX7 was expressed in 27 of 30 Ewing sarcomas (90%), mainly in a diffuse and strong manner. Although NKX2-2 showed similar sensitivity, PAX7 showed more extensive and strong reactivity....
Histopathology, Jan 19, 2018
Sessile serrated adenoma/polyp (SSA/P) is regarded as a genetically homogeneous entity, with most... more Sessile serrated adenoma/polyp (SSA/P) is regarded as a genetically homogeneous entity, with most lesions harbouring the BRAF V600E mutation. The present study aimed to reappraise the genetic heterogeneity of SSA/Ps and its clinicopathological significance. We performed next-generation sequencing of 272 SSA/Ps without dysplasia and evaluated morphological and molecular features associated with the respective genotypes. BRAF V600E, BRAF non-V600E, KRAS and NRAS mutations were found in 223 (82.0%), three (1.2%), 28 (10.3%) and one lesion (0.4%), respectively. Notably, all lesions with BRAF non-V600E mutations had either KRAS or NRAS mutations concurrently. Twenty SSA/Ps (7.4%) were negative for these mutations. KRAS-mutated SSA/Ps were located more often in the distal colon (42%) compared to those with the BRAF V600E mutation (14%). Histologically, minimally serrated crypts and goblet cell-rich crypts were more common in KRAS-mutated and mutation-negative SSA/Ps. However, in most inst...
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, Jan 22, 2018
We describe a series of colorectal polyps characterized by mixed adenomatous and serrated feature... more We describe a series of colorectal polyps characterized by mixed adenomatous and serrated features, herein referred to as superficially serrated adenomas. Twenty superficially serrated adenomas were obtained from 11 female and 9 male patients aged 62-87 years. Most lesions endoscopically appeared as small sessile polyps, but larger lesions were plaque-like (2-20 mm; median, 5 mm). Eighteen lesions (90%) were located in the sigmoid colon or rectum. They consisted primarily of straight, adenomatous glands but showed serration confined to the superficial layer. Immunohistochemistry revealed CK20 expression in the upper layer. Proliferating cells, determined by their expression of Ki-67, were localized to the middle to bottom layers. Genetic analyses identified KRAS mutations in 19 lesions and a BRAF mutation in one lesion. Furthermore, RSPO fusions and/or overexpression were observed in 18 lesions and truncating APC mutations were observed in the two remaining lesions. Consistent with ...