Cheng-Lin Wu | National Cheng Kung University (original) (raw)

Papers by Cheng-Lin Wu

BMC Oral Health

Background Morphological evaluation of oral mucosal biopsy is sometimes inconclusive, which may d... more Background Morphological evaluation of oral mucosal biopsy is sometimes inconclusive, which may delay the diagnosis and treatment of oral squamous malignancy. Immunohistochemical biomarkers denoting oral squamous malignancy would be clinically helpful in such scenario. Methods We first studied the expression patterns of four potential biomarkers (cytokeratin 13, cytokeratin 17, Ki-67 and laminin 5 gamma 2 chain) in an exploratory cohort containing 54 surgical specimens from confirmed oral squamous malignancies. A pattern score was assigned to each specific expression pattern of these four biomarkers. A total score from each specimen was then calculated by summing up the four pattern scores. A cut-off value of total score denoting oral squamous malignancy was then determined. Another 34 oral squamous malignancies that were misdiagnosed as non-malignant lesions on their pre-treatment biopsies were used as a validation cohort to test the clinical utility of this scoring system. Results...

胸腔醫學, Aug 1, 2014

Pulmonary sarcomatoid carcinoma is a rare form of non-small cell lung cancer that comprises 0.1% ... more Pulmonary sarcomatoid carcinoma is a rare form of non-small cell lung cancer that comprises 0.1% to 0.4% of all lung malignancies. Patients are predominantly male smokers with a median age of 60 to 70 years. The clinical course is aggressive and the prognosis is significantly worse than that of other forms of non-small cell lung cancer. Pulmonary sarcomatoid carcinoma usually presents as a large, solitary, peripheral mass with chest wall invasion, and very rarely as a protruding endobronchial tumor with pulmonary vessel invasion. We report the case of a 59-year-old female non-smoker with the unusual presentation of pulmonary sarcomatoid carcinoma (subtype spindle cell carcinoma) as an endobronchial mass obstructing the left main bronchus and invading the left pulmonary artery.

Scientific Reports

Bone morphogenetic protein 2 (BMP2) is highly overexpressed in human non-small cell lung cancer (... more Bone morphogenetic protein 2 (BMP2) is highly overexpressed in human non-small cell lung cancer (NSCLC) and correlates with tumor stage and metastatic burden. Although several lines of evidence suggest that BMP2 promotes cell migration and invasiveness in vitro, the in vivo role of BMP2 in the metastasis of lung adenocarcinoma cells remains less well understood. Here, we revealed that BMP2 is highly overexpressed in lung adenocarcinoma patients with lymph node metastasis compared with patients without lymph node metastasis. Using an in vivo orthotopic mouse model, we clearly demonstrated that BMP2 promotes lung adenocarcinoma metastasis. The depletion of BMP2 or its receptor BMPR2 significantly reduced cell migration and invasiveness. We further identified that BMP2/BMPR2-mediated cell migration involves the activation of the SMAD1/5/8 signaling pathway, independent of the KRAS signaling pathway. Significantly, the depletion of SMAD1/5/8 or the inhibition of SMAD1/5/8 by LDN193189 i...

Clinical Endoscopy

Endoscopic ultrasonography (EUS)-guided tissue acquisition (TA) has evolved as an important tool ... more Endoscopic ultrasonography (EUS)-guided tissue acquisition (TA) has evolved as an important tool for diagnosing gastrointestinal tract subepithelial mass lesion and pancreatobili-ary disease since the first report of EUS fine needle aspiration (FNA) by Vilmann et al. in 1992. 1 Because of its high sensitivity, specificity, accuracy, and relatively lower complication rate, EUS TA had gradually replaced the percutaneous and surgical TA in this field, and has become the standard procedure in

The most significant 122 genes associated with pancreatic invasion were analyzed by IPA6.0. Gene ... more The most significant 122 genes associated with pancreatic invasion were analyzed by IPA6.0. Gene network was represented as nodes and lines between two nodes. Node shapes symbolized the functional class of the gene product: inverted bell, cytokine and growth factor; hook, enzyme; trefoil, kinase; dumbbells, transcription regulator; upward scoop, transmembrane receptor; circle, complex or other. The bar graph right to the particular molecules depicted as the relative fold change of the particular gene and the bar from left to right was represented as patient 1 to 5. The log ratio of fold change in gene expression was represented as number under the particular molecules. The intensity of node colors indicated the degree of upregulation (red) or downregulation (green) in ampullary cancer than normal duodenum. Continuous and dashed lines indicated direct and indirect interactions between molecules, respectively. Bold nodes with blue rims represented genes associated with EMT or colorect...

American journal of cancer research, 2021

In spite of radio- and chemotherapy, glioblastoma (GBM) develops therapeutic resistance leading t... more In spite of radio- and chemotherapy, glioblastoma (GBM) develops therapeutic resistance leading to recurrence and poor prognosis. Therefore, understanding the underlying mechanisms of resistance is important to improve the treatment of GBM. To this end, we developed a radiation-resistant cell model by exposure to consecutive periods of irradiation. Simultaneously, single high-dose irradiation was introduced to determine "when" GBM developed consecutive irradiation-induced resistance (CIIR). We found that CIIR promoted TGF-β secretion, activated pro-survival Akt, and downregulated p21 in a p53-independent manner. Furthermore, CIIR upregulated multidrug-resistant proteins, resulting in temozolomide resistance. CIIR GBM also enhanced cell mobility and accelerated cell proliferation. The big-conductance calcium-activated potassium channel (BK channel) is highly expressed and activated in GBM. However, CIIR diminishes BK channel activity in an expression-independent manner. Cil...

Life, 2021

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is the most common cause of mortality ... more Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is the most common cause of mortality and neurological disability in infancy after perinatal asphyxia. Reliable biomarkers to predict neurological outcomes of neonates after perinatal asphyxia are still not accessible in clinical practice. Methods: A prospective cohort study enrolled neonates with perinatal asphyxia. Biochemical blood tests and cerebral Doppler ultrasound were measured within 6 h of age and at the 4th day old. Neurological outcomes were assessed at 1 year old. Results: Sixty-four neonates with perinatal asphyxia were enrolled. Fifty-eight (90%) had hypoxic-ischemic encephalopathy (HIE) including 20 (34%) Stage I, 21 (36%) Stage II, and 17 (29%) Stage III. In the asphyxiated infants without therapeutic hypothermia, HIE stage, PH, and base excess levels within 6 h of age were the predictors of adverse outcomes. In the asphyxiated infants receiving therapeutic hypothermia, HIE stage failed to predict outcomes. ...

International Journal of Molecular Sciences, 2021

Despite neurosurgery following radiation and chemotherapy, residual glioblastoma (GBM) cells deve... more Despite neurosurgery following radiation and chemotherapy, residual glioblastoma (GBM) cells develop therapeutic resistance (TR) leading to recurrence. The GBM heterogeneity confers TR. Therefore, an effective strategy must target cancer stem cells (CSCs) and other malignant cancer cells. TGF-β and mesenchymal transition are the indicators for poor prognoses. The activity of aldehyde dehydrogenases (ALDHs) is a functional CSC marker. However, the interplay between TGF-β and ALDHs remains unclear. We developed radiation-resistant and radiation-temozolomide-resistant GBM models to investigate the underlying mechanisms conferring TR. Galunisertib is a drug targeting TGF-β receptors. Disulfiram (DSF) is an anti-alcoholism drug which functions by inhibiting ALDHs. The anti-tumor effects of combining DSF and Galunisertib were evaluated by in vitro cell grow, wound healing, Transwell assays, and in vivo orthotopic GBM model. Mesenchymal-like phenotype was facilitated by TGF-β in TR GBM. Ad...

American Journal of Clinical Pathology, 2020

Objectives Merkel cell carcinoma is a rare but very aggressive cutaneous tumor. We evaluated the ... more Objectives Merkel cell carcinoma is a rare but very aggressive cutaneous tumor. We evaluated the prognostic potential of B-cell markers (terminal deoxynucleotidyl transferase [TdT], PAX5, CD117), follicular stem cell markers (CK15, CK19), p63, p53, RB, and Merkel cell polyomavirus (MCPyV; CM2B4) in 136 primary cutaneous Merkel cell carcinomas. Methods Clinical, histopathologic, and immunohistochemical analyses were performed. The results were correlated with patient outcomes by Fisher exact test, log-rank tests, and Cox multivariate models. Results By Fisher exact test, although TdT significantly correlated with both lack of progression (P = .0087) and alive status (P = .0056), MCPyV status correlated only with alive status (P = .031). In univariate analyses, TdT, MCPyV, and RB significantly correlated with improved overall survival, whereas p63 and CK15 correlated with worse overall survival. However, in multivariate analyses, only TdT expression remained as an independent predicto...

Kaohsiung Journal of Medical Sciences, Feb 16, 2023

A wide variety of primary and secondary lymphoma types involves the skin. However, reports with c... more A wide variety of primary and secondary lymphoma types involves the skin. However, reports with comparisons between both groups are limited in Taiwan. We retrospectively enrolled all cutaneous lymphomas and evaluated their clinicopathologic features. There were 221 cases of lymphoma: 182 (82.3%) primary and 39 (17.7%) secondary. Mycosis fungoides was the most common primary T-cell lymphoma, 92 (41.7%) cases, followed by CD30-positive T-cell lymphoproliferative disorders including lymphomatoid papulosis (n = 33, 14.9%) and cutaneous anaplastic large cell lymphoma (n = 12, 5.4%). The most frequent primary B-cell lymphomas were marginal zone lymphoma (n = 8, 3.6%) and diffuse large B-cell lymphoma (DLBCL), leg type (n = 8, 3.6%). DLBCL including variants was the most common secondary lymphoma involving skin. Most primary lymphomas presented at low-stage (T-cell, 86%; B-cell, 75%), whereas the majority of secondary lymphomas presented at high-stage (T-cell, 94%; B-cell, 100%). Patients with secondary lymphomas had an older mean age, more frequent B symptoms, lower serum albumin and hemoglobin, and a higher frequency of atypical lymphocytes in blood than those with primary lymphomas. In primary lymphomas, older age, lymphoma types, decreased lymphocyte counts and atypical lymphocytes in blood were poorer prognostic factors. In secondary lymphoma patients, lymphoma types, high serum lactate dehydrogenase and low hemoglobin levels predicted poorer survival. We found that the distribution of primary cutaneous lymphomas in Taiwan mirrors that of other Asian countries but shows some differences as compared with Western countries. Primary cutaneous lymphomas have a better prognosis than secondary lymphomas. Histologic classification of lymphomas highly correlated with disease presentation and prognosis.

Cells, 2020

Introduction: Mucosal melanoma is rare and associated with poorer prognosis in comparison to conv... more Introduction: Mucosal melanoma is rare and associated with poorer prognosis in comparison to conventional melanoma subtypes. Little is known about the prognostic significance as well as possible associations between PARP1 and immunologic response in mucosal melanoma. Methods: PARP1, PD-L1 and IDO1 immunostains were performed on 192 mucosal melanomas including 86 vulvar, 89 sinonasal, and 17 anorectal melanomas. Results: By Kaplan–Meier analyses, high PARP1 expression correlated with worse overall and melanoma-specific survival (log-rank p values = 0.026 and 0.047, respectively). Tumors with combined PARP1 and IDO1 high expression correlated with worse overall and melanoma-specific survival (p = 0.015, 0.0034 respectively). By multivariate analyses, high PARP1 expression remained a predictor of worse survival independent of stage. By Fisher’s exact test, high PARP1 expression correlated with highly mitogenic tumors (p = 0.02). High tumoral PD-L1 and IDO1 expression were associated wi...

IEEE Transactions on Biomedical Engineering

To identify the turbulent components of blood flow facilitating aortic lumen dilatation in a post... more To identify the turbulent components of blood flow facilitating aortic lumen dilatation in a post-stenotic dilatation (PSD) porcine model. Methods: The porcine abdominal aorta (AA) was moderately coarctated to induce overt flow turbulence in the downstream region and to lead to dilatation in time periods between four and twelve weeks. We propose a new metric, fluctuation intensity (FI), to quantify turbulent fluctuations of pulsatile aortic flow measured within twenty minutes post-coarctation. Lumen perimeter ratio (LPR) of the distal-to-suprarenal AA was used to assess the degree of PSD. Using k-means clustering analysis, we first divided FI frequency spectrum into low-and high-frequency fluctuation intensity (LFFI and HFFI), and subsequently grouped animals with coarctation. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of the proposed metric to predict PSD. Results: The frequency band of the FI spectrum in facilitating aortic lumen dilatation was identified to be 40∼200 Hz. Using sham group as the reference, pigs receiving coarctation were clustered into two groups with (group A) and without (group B) increases in HFFI values. Coarctation significantly increased LPR values in group A, but not in group B. Moreover, group A exhibited a high probability density distribution on severe elastic fiber fragmentation. ROC analysis indicated HFFI to be capable of predicting PSD with excellent sensitivity and specificity. Conclusion: High-intensity, high-frequency components of

Indian Dermatology Online Journal

© 2018 Indian Dermatology Online Journal | Published by Wolters Kluwer Medknow A 75-year-old fema... more © 2018 Indian Dermatology Online Journal | Published by Wolters Kluwer Medknow A 75-year-old female presented to our clinic complaining of a very painful lesion in the vulva area for more than 1 month. Examination revealed a 1-cm, round erythematous erosion on the left vulva [Figure 1]. KOH smear revealed presence of pseudohyphae and budding yeast forms, indicating candidiasis. The symptoms improved after topical antifungal treatment. A skin biopsy specimen of the erosion revealed an extensive intraepidermal infiltration of atypical cells with hyperchromatic pleomorphic nuclei [Figure 2]. The tumor cells were melan‐A (‒),

The most significant 122 genes associated with pancreatic invasion were analyzed by IPA6.0. Major... more The most significant 122 genes associated with pancreatic invasion were analyzed by IPA6.0. Major canonical pathways of disease bio-functions were listed and cellular movement was the first one. (TIFF 993 kb)

Cancers, 2021

Background: Merkel cell carcinomas of unknown primary (MCC-UPs) are defined as deep-seated tumors... more Background: Merkel cell carcinomas of unknown primary (MCC-UPs) are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. Methods: We compared the immunohistochemical profiles of four groups of MCCs (Merkel cell polyomavirus (MCPyV)-positive UP, MCPyV-negative UP, MCPyV-positive known primary (KP), and MCPyV-negative KP) using B-cell and pre-B-cell markers, cell cycle regulating proteins, follicular stem cell markers, and immune markers, and performed next generation and Sanger sequencing. Results: Virus-positive and virus-negative MCC-UPs exhibited an immunoprofile similar to virus-positive and virus-negative primary cutaneous MCCs, respectively. MCC-UP tumors (both virus-positive and -negative) were immunogenic with similar or even higher tumoral PD-L1 expression and intratumoral CD8 and FoxP...

The American Journal of Dermatopathology, 2020

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of unknown o... more Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of unknown origin. We performed a retrospective histologic review of primary cutaneous MCCs diagnosed from 1997 to 2018 in several clinical institutions and literature review to determine the frequency of various unusual morphologic appearances of MCC. Of the 136 primary MCCs identified, intraepidermal carcinoma or epidermotropism was noted in 11/136 (8%) cases. An association with pilar cyst in 1/136 (0.7%) case, with actinic keratosis in 2/136 (1.5%) cases, with either invasive or in situ squamous cell carcinoma (SCC) in 14/136 (10%) cases, with poroma in 1/136 (0.7%), and with basal cell carcinoma in 1/136 (0.7%) case was noted. Trabecular pattern and rosettes were noted in 7/136 (5%) and 3/136 (2%) cases, respectively. There was one case of metastatic MCC in a lymph node with chronic lymphocytic leukemia and one rare case of metastatic MCC and SCC in a lymph node. Although uncommon, differentiation toward other cell lineage can be observed in both primary and metastatic MCCs. The tumor can assume a variety of histologic appearances including association with SCC, basal cell carcinoma, melanocytic neoplasm, and follicular cyst; as well as exhibit glandular, sarcomatous, and mesenchymal differentiation. This diversity of morphologic appearance of MCC reflects the complexity of its underlying pathogenesis.

Modern Pathology, 2021

TO THE EDITOR: We read with great interest the recent article “Superficial ALKrearranged myxoid s... more TO THE EDITOR: We read with great interest the recent article “Superficial ALKrearranged myxoid spindle cell neoplasm: a cutaneous soft tissue tumor with distinctive morphology and immunophenotypic profile” by Dermawan et al., describing a series of six cases with ALK gene fusions, including FLNA-ALK, MYH10-ALK, and HMBOX1-ALK, and a peculiar histomorphology of spindle to ovoid cells forming whorls or cord-like arrangements in a background of myxoid to myxohyaline matrix. Rather than fitting into well-established tumor entities with ALK gene fusions, such as inflammatory myofibroblastic tumor, epithelioid fibrous histiocytoma, or spitzoid melanocytic tumors, these tumors show a certain degree of overlap with mesenchymal tumors harboring NTRK or other tyrosine kinase gene fusion by expression of CD34 and/or S100 and the occasional findings of lipofibromatosis-like pattern, perivascular hyalinization, and intratumoral lymphocytes. Nevertheless, the unique histologic features of concentric whorls and cord-like arrangements in these tumors are unorthodox in typical NTRK-fused mesenchymal tumors. With only limited cases reported in a single series to date, the histologic and molecular spectrum of these superficial ALKrearranged myxoid spindle cell neoplasms remains to be explored. Here we report a large subcutaneous tumor with a predominantly reticular to cord-like pattern and a novel FMR1-ALK fusion. Our patient was a 37-year-old female presenting with an enlarging subcutaneous tumor in the left buttock for more than 1 year. Ultrasound examination revealed a lobulated and hypoechoic mass with some hyperechoic streaks in the deep subcutaneous tissue abutting fascia. Grossly, it was a lobulated and relatively well-defined tumor measuring about 11 × 5 cm in dimensions (Fig. 1A). Microscopically, the tumor was composed of relatively uniform tumor cells with round to ovoid nuclei, arranged in reticular and cord-like patterns in a myxohyaline stroma (Fig. 1B, C). The tumor cells had fine chromatin, scant cytoplasm, and occasional intranuclear pseudoinclusions (Fig. 1D). Ectatic thinwalled vessels were present throughout the tumor, and perivascular hyalinization or edema was present in some of the vessels (Fig. 1E). As a minor component, small cellular aggregates with whorl-like arrangements of the tumor cells were also seen focally (Fig. 1F). No significant lymphocytic infiltrate or lipofibromatosislike area was observed. Mitotic activity was very low, if any, and no tumor necrosis was found. Immunohistochemically, the tumor cells exhibited strong but patchy expression of CD34 (40%, Fig. 2A) and focal reactivity to S100 (10%, Fig. 2B), while CK (AE1/AE3), LMW-CK, EMA, SOX10, SMA, GFAP, claudin-1, MUC4, STAT6, BCOR, and pan-Trk were all negative. With the differential diagnosis of myoepithelial tumor, ossifying fibromyxoid tumor, and OGTrearranged mesenchymal neoplasm in mind, fluorescence in situ hybridization (FISH) assays for EWSR1, FUS, PHF1, BCOR, OGT, and FOXO1 rearrangements were performed and all showed negative results. RNA sequencing using TruSeq RNA Exome (Illumina) revealed a novel FMR1-ALK fusion joining exon 17 of FMR1 (midexonic breakpoint) to exon 20 of ALK, which was subsequently validated by reverse transcription-polymerase chain reaction with Sanger sequencing and by break-apart FISH assays, demonstrating rearranged ALK and FMR1, respectively (Fig. 2C–E). The fusion transcript was predicted to be in-frame and, like most ALK gene fusions, preserved the sequence encoding the receptor tyrosine kinase domain of ALK. Immunohistochemical stain for ALK (D5F3) exhibited diffuse and strong ALK reactivity (Fig. 2F). The tumor was marginally excised with positive margins. The patient had no local recurrence 9 months after the surgery. Compared to the previously reported case series, our case had the largest tumor size (11 cm) and relatively limited extent of S100 staining. The proportions of different histologic patterns are not specified in the previous study. Our case showed a predominantly reticular to cord-like arrangement and only focal presence of the distinct whorl-like pattern, hence morphologically mimicking myoepithelial tumor, ossifying fibromyxoid tumor, sclerosing epithelioid fibrosarcoma, and OGT-rearranged mesenchymal tumor. Aside from focal S100 expression, other myoepithelial markers, such as CK (AE1/AE3), EMA, and GFAP, were negative in our case. It also lacked the ossified matrix and PHF1 or BCOR rearrangements characteristic of ossifying fibromyxoid tumor. Negative MUC4 expression and lack of EWSR1 and FUS rearrangements did not support the diagnosis of sclerosing epithelioid fibrosarcoma. Similar to these superficial ALK-rearranged tumors, OGT-rearranged mesenchymal tumors also show a biphasic pattern with cord-like and whorled arrangements of tumor cells in a myxohyaline to fibromyxoid stroma, accompanied by perivascular hyalinization, and are immunoreactive to CD34. However,…

Table S1.Primers used for reverse transcription polymerase chain reaction (RT-PCR). Table S2. Fiv... more Table S1.Primers used for reverse transcription polymerase chain reaction (RT-PCR). Table S2. Five pairs of fresh cancer tissues and corresponding normal duodenal mucosa were examined using a cDNA microarray. Here are the demographics, pathologic stage, clinical outcomes, histological type, and CD44s expression of the five patients. (DOC 43 kb)