Kenneth Shroyer | SUNY: Stony Brook University (original) (raw)
Uploads
Papers by Kenneth Shroyer
Obstetrics & Gynecology, Jun 1, 2001
Journal of the Neurological Sciences, Dec 1, 1998
American Journal of Clinical Pathology, Sep 1, 1995
Polymerase chain reaction (PCR) and in situ hybridization were used to test for the presence of h... more Polymerase chain reaction (PCR) and in situ hybridization were used to test for the presence of human papillomavirus (HPV) DNA in cases of anorectal squamous cell carcinoma. Human papillomavirus was detected by PCR with L1 consensus sequence primers in 22 of 27 cases, including 10 of 11 cases with a prominent basaloid pattern and 12 of 16 cases without basaloid patterns of differentiation. Slot blot hybridization identified HPV type 16 as the most common type, present in 7 of 10 cases of basaloid carcinoma and 10 of 12 cases without basaloid features. In situ hybridization confirmed the presence of HPV in tumor cell nuclei of five cases of basaloid carcinoma and in eight cases of squamous cell carcinoma without basaloid pattern. The authors conclude that the prevalence of HPV in cases of anorectal squamous cell carcinoma is unrelated to the presence or absence of a basaloid pattern of differentiation.
Journal of the American Society of Cytopathology, Sep 1, 2021
Archives of Pathology & Laboratory Medicine, Jul 1, 2003
Survivin is a novel inhibitor of apoptosis that acts via a pathway independent of bcl-2. Little i... more Survivin is a novel inhibitor of apoptosis that acts via a pathway independent of bcl-2. Little is known about its distribution in brain tumors or how it correlates with other biomarkers of malignancy, such as telomerase, an enzyme that plays a critical role in cellular immortalization and cancer biology. To assess survivin protein expression in gliomas and to compare expression with that of telomerase. Immunohistochemical staining for survivin protein expression was performed using an antibody developed in our laboratory. Quantitative survivin messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction. In selected cases, survivin results were compared with quantitative telomerase values analyzed by polymerase chain reaction-based telomerase repeat amplification protocol (TRAP) assay. Twenty-five tumor tissue samples from 16 cases of glioblastoma multiforme (GBM; including multiple tissue samples in 6 patients), 2 grade II gliomas, 4 grade III gliomas, and 3 control temporal lobectomy specimens were studied. Nuclear immunoreactivity for survivin protein and survivin mRNA were detectable in most glioma samples, regardless of grade. Glioblastoma multiforme demonstrated moderate protein expression and survivin mRNA levels compared to epithelial malignancies previously tested in our laboratory. Although the association of survivin mRNA with the levels of telomerase within the GBM cases did not reach statistical significance, most GBMs also expressed survivin. The quantitative score for survivin mRNA was higher in GBMs than in grade II and III gliomas (P =.02), after accounting for multiple specimens per patient. Quantitative survivin mRNA analysis, but not immunohistochemistry, distinguished GBMs from lower grade gliomas. Mechanisms that promote both cell proliferation (telomerase expression) and cell survival (survivin expression) are often activated in GBMs.
Applied Immunohistochemistry & Molecular Morphology, Jun 1, 2002
Journal of Clinical Oncology, Jul 1, 1999
Telomerase has been detected in a majority of human malignant tumors, making telomerase activity ... more Telomerase has been detected in a majority of human malignant tumors, making telomerase activity (TA) one key difference between mortal and immortal cells. In this study, we evaluated in blind-trial fashion the association of TA with cytologic and final clinical/pathologic diagnosis in fine-needle aspirates (FNAs) of breast lesions. In 172 FNAs, including 80 samples that were cytologically malignant, 18 that were atypical but not diagnostic for malignancy, and 74 that were cytologically benign, TA was determined by a modified nonradioactive telomeric repeat amplification protocol (TRAP) assay. Final diagnosis was made by pathologic examination of follow-up surgical material available for all the cytologically malignant samples, a majority of the cytologically atypical samples, and a portion of the cytologically benign samples. TA was detected in 85 of 172 samples. Comparison of the cytologic and histologic diagnoses with TA showed that 80 of 87 samples from patients with breast cancer were telomerase-positive, resulting in a sensitivity of 92%. TA was found in four of five FNAs from carcinomas that were considered cytologically atypical but not diagnostic for malignancy. Eighty of 85 samples from patients with benign breast lesions were telomerase-negative, revealing a specificity of 94%. The five positive cases in this group were all fibroadenomas with low TA. Among the 18 cases with a cytologic diagnosis of atypia, there was a strong positive relationship between TRAP findings and histologic diagnosis. The detection of TA in FNAs of breast lesions is a highly sensitive and specific marker of malignancy and may be used as an adjunct in cases with an equivocal cytologic diagnosis.
Obstetrics & Gynecology, Jun 1, 2001
Gynecologic Oncology, 2002
In the current study, the quantitative levels of telomerase hTERT mRNA and the functional telomer... more In the current study, the quantitative levels of telomerase hTERT mRNA and the functional telomerase repeat amplification protocol (TRAP) assay were correlated with tumor grade in endometrial carcinomas and with the histologic phase of normal endometrium. Twenty-six samples of endometroid adenocarcinoma and 20 cases of benign endometrium were obtained from hysterectomy specimens. Total RNA was extracted from each tissue sample and used for quantitative real-time RT-PCR of hTERT mRNA and the levels were standardized to the levels of ribosomal RNA. Quantitative determination of telomerase activity was performed by the polymerase chain-based TRAP assay and the levels of expression were defined by the ratio of radioactivity incorporated into the 6-bp telomerase amplification products versus the radioactivity incorporated into an internal standard (telomerase/ITAS x 100 = 1 RU). Statistical analyses were performed using the Fisher exact test or chi2 test, a Wilcoxon rank sum test, and a linear regression analysis. hTERT mRNA and telomerase activity levels showed a linear association in the study group (P = 0.006, R2 = 0.139). hTERT mRNA levels and telomerase activity levels were significantly higher in endometrial cancer (179 pg/ng rRNA, 44 relative units (RU)) than in normal endometrium (45 pg/ng), (15 RU) (P = 0.009, P = 0.006). In normal endometrium, hTERT mRNA and telomerase activity levels were highest in the proliferative phase (74 pg/ng rRNA, 25 RU) and were relatively low in secretory (13 pg/ng rRNA, 6 RU) and atrophic endometrium (9 pg/ng rRNA, 2 RU). These results suggest that the quantitative analysis of hTERT and telomerase activity may have potential roles as diagnostic or prognostic adjuncts for both premenopausal and postmenopausal patients with endometrial cancer.
Archives of Pathology & Laboratory Medicine, Jul 1, 2003
Journal of Cutaneous Pathology, 1997
ABSTRACT
Human Pathology, Apr 1, 2004
Academic Pathology, 2021
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unpr... more The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unprecedented need for comprehensive laboratory testing of populations, in order to meet the needs of medical practice and to guide the management and functioning of our society. With the greater New York metropolitan area as an epicenter of this pandemic beginning in March 2020, a consortium of laboratory leaders from the assembled New York academic medical institutions was formed to help identify and solve the challenges of deploying testing. This report brings forward the experience of this consortium, based on the real-world challenges which we encountered in testing patients and in supporting the recovery effort to reestablish the health care workplace. In coordination with the Greater New York Hospital Association and with the public health laboratory of New York State, this consortium communicated with state leadership to help inform public decision-making addressing the crisis. Throu...
Diagnostic Pathology, 2020
Background Multiplex immunohistochemistry (mIHC) permits the labeling of six or more distinct cel... more Background Multiplex immunohistochemistry (mIHC) permits the labeling of six or more distinct cell types within a single histologic tissue section. The classification of each cell type requires detection of uniquely colored chromogens localized to cells expressing biomarkers of interest. The most comprehensive and reproducible method to evaluate such slides is to employ digital pathology and image analysis pipelines to whole-slide images (WSIs). Our suite of deep learning tools quantitatively evaluates the expression of six biomarkers in mIHC WSIs. These methods address the current lack of readily available methods to evaluate more than four biomarkers and circumvent the need for specialized instrumentation to spectrally separate different colors. The use case application for our methods is a study that investigates tumor immune interactions in pancreatic ductal adenocarcinoma (PDAC) with a customized mIHC panel. Methods Six different colored chromogens were utilized to label T-cell...
Mucosal Immunology, 2020
Interleukin-22 (IL-22) signaling in the intestines is critical for promoting tissue-protective fu... more Interleukin-22 (IL-22) signaling in the intestines is critical for promoting tissue-protective functions. However, since a diverse array of cell types (absorptive and secretory epithelium as well as stem cells) express IL-22Ra1, a receptor for IL-22, it has been difficult to determine what cell type(s) specifically respond to IL-22 to mediate intestinal mucosal host defense. Here, we report that IL-22 signaling in the small intestine is positively correlated with Paneth cell differentiation programs. Our Il22Ra1fl/fl;Lgr5-EGFP-creERT2-specific knockout mice and, independently, our lineage-tracing findings rule out the involvement of Lgr5+ intestinal stem cell (ISC)-dependent IL-22Ra1 signaling in regulating the lineage commitment of epithelial cells, including Paneth cells. Using novel Paneth cell-specific IL-22Ra1 knockout mice (Il22Ra1fl/fl;Defa6-cre), we show that IL-22 signaling in Paneth cells is required for small intestinal host defense. We show that Paneth cell maturation, a...
Diagnostic Pathology, 2020
An amendment to this paper has been published and can be accessed via the original article.
British Journal of Cancer, 2020
Obstetrics & Gynecology, Jun 1, 2001
Journal of the Neurological Sciences, Dec 1, 1998
American Journal of Clinical Pathology, Sep 1, 1995
Polymerase chain reaction (PCR) and in situ hybridization were used to test for the presence of h... more Polymerase chain reaction (PCR) and in situ hybridization were used to test for the presence of human papillomavirus (HPV) DNA in cases of anorectal squamous cell carcinoma. Human papillomavirus was detected by PCR with L1 consensus sequence primers in 22 of 27 cases, including 10 of 11 cases with a prominent basaloid pattern and 12 of 16 cases without basaloid patterns of differentiation. Slot blot hybridization identified HPV type 16 as the most common type, present in 7 of 10 cases of basaloid carcinoma and 10 of 12 cases without basaloid features. In situ hybridization confirmed the presence of HPV in tumor cell nuclei of five cases of basaloid carcinoma and in eight cases of squamous cell carcinoma without basaloid pattern. The authors conclude that the prevalence of HPV in cases of anorectal squamous cell carcinoma is unrelated to the presence or absence of a basaloid pattern of differentiation.
Journal of the American Society of Cytopathology, Sep 1, 2021
Archives of Pathology & Laboratory Medicine, Jul 1, 2003
Survivin is a novel inhibitor of apoptosis that acts via a pathway independent of bcl-2. Little i... more Survivin is a novel inhibitor of apoptosis that acts via a pathway independent of bcl-2. Little is known about its distribution in brain tumors or how it correlates with other biomarkers of malignancy, such as telomerase, an enzyme that plays a critical role in cellular immortalization and cancer biology. To assess survivin protein expression in gliomas and to compare expression with that of telomerase. Immunohistochemical staining for survivin protein expression was performed using an antibody developed in our laboratory. Quantitative survivin messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction. In selected cases, survivin results were compared with quantitative telomerase values analyzed by polymerase chain reaction-based telomerase repeat amplification protocol (TRAP) assay. Twenty-five tumor tissue samples from 16 cases of glioblastoma multiforme (GBM; including multiple tissue samples in 6 patients), 2 grade II gliomas, 4 grade III gliomas, and 3 control temporal lobectomy specimens were studied. Nuclear immunoreactivity for survivin protein and survivin mRNA were detectable in most glioma samples, regardless of grade. Glioblastoma multiforme demonstrated moderate protein expression and survivin mRNA levels compared to epithelial malignancies previously tested in our laboratory. Although the association of survivin mRNA with the levels of telomerase within the GBM cases did not reach statistical significance, most GBMs also expressed survivin. The quantitative score for survivin mRNA was higher in GBMs than in grade II and III gliomas (P =.02), after accounting for multiple specimens per patient. Quantitative survivin mRNA analysis, but not immunohistochemistry, distinguished GBMs from lower grade gliomas. Mechanisms that promote both cell proliferation (telomerase expression) and cell survival (survivin expression) are often activated in GBMs.
Applied Immunohistochemistry & Molecular Morphology, Jun 1, 2002
Journal of Clinical Oncology, Jul 1, 1999
Telomerase has been detected in a majority of human malignant tumors, making telomerase activity ... more Telomerase has been detected in a majority of human malignant tumors, making telomerase activity (TA) one key difference between mortal and immortal cells. In this study, we evaluated in blind-trial fashion the association of TA with cytologic and final clinical/pathologic diagnosis in fine-needle aspirates (FNAs) of breast lesions. In 172 FNAs, including 80 samples that were cytologically malignant, 18 that were atypical but not diagnostic for malignancy, and 74 that were cytologically benign, TA was determined by a modified nonradioactive telomeric repeat amplification protocol (TRAP) assay. Final diagnosis was made by pathologic examination of follow-up surgical material available for all the cytologically malignant samples, a majority of the cytologically atypical samples, and a portion of the cytologically benign samples. TA was detected in 85 of 172 samples. Comparison of the cytologic and histologic diagnoses with TA showed that 80 of 87 samples from patients with breast cancer were telomerase-positive, resulting in a sensitivity of 92%. TA was found in four of five FNAs from carcinomas that were considered cytologically atypical but not diagnostic for malignancy. Eighty of 85 samples from patients with benign breast lesions were telomerase-negative, revealing a specificity of 94%. The five positive cases in this group were all fibroadenomas with low TA. Among the 18 cases with a cytologic diagnosis of atypia, there was a strong positive relationship between TRAP findings and histologic diagnosis. The detection of TA in FNAs of breast lesions is a highly sensitive and specific marker of malignancy and may be used as an adjunct in cases with an equivocal cytologic diagnosis.
Obstetrics & Gynecology, Jun 1, 2001
Gynecologic Oncology, 2002
In the current study, the quantitative levels of telomerase hTERT mRNA and the functional telomer... more In the current study, the quantitative levels of telomerase hTERT mRNA and the functional telomerase repeat amplification protocol (TRAP) assay were correlated with tumor grade in endometrial carcinomas and with the histologic phase of normal endometrium. Twenty-six samples of endometroid adenocarcinoma and 20 cases of benign endometrium were obtained from hysterectomy specimens. Total RNA was extracted from each tissue sample and used for quantitative real-time RT-PCR of hTERT mRNA and the levels were standardized to the levels of ribosomal RNA. Quantitative determination of telomerase activity was performed by the polymerase chain-based TRAP assay and the levels of expression were defined by the ratio of radioactivity incorporated into the 6-bp telomerase amplification products versus the radioactivity incorporated into an internal standard (telomerase/ITAS x 100 = 1 RU). Statistical analyses were performed using the Fisher exact test or chi2 test, a Wilcoxon rank sum test, and a linear regression analysis. hTERT mRNA and telomerase activity levels showed a linear association in the study group (P = 0.006, R2 = 0.139). hTERT mRNA levels and telomerase activity levels were significantly higher in endometrial cancer (179 pg/ng rRNA, 44 relative units (RU)) than in normal endometrium (45 pg/ng), (15 RU) (P = 0.009, P = 0.006). In normal endometrium, hTERT mRNA and telomerase activity levels were highest in the proliferative phase (74 pg/ng rRNA, 25 RU) and were relatively low in secretory (13 pg/ng rRNA, 6 RU) and atrophic endometrium (9 pg/ng rRNA, 2 RU). These results suggest that the quantitative analysis of hTERT and telomerase activity may have potential roles as diagnostic or prognostic adjuncts for both premenopausal and postmenopausal patients with endometrial cancer.
Archives of Pathology & Laboratory Medicine, Jul 1, 2003
Journal of Cutaneous Pathology, 1997
ABSTRACT
Human Pathology, Apr 1, 2004
Academic Pathology, 2021
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unpr... more The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unprecedented need for comprehensive laboratory testing of populations, in order to meet the needs of medical practice and to guide the management and functioning of our society. With the greater New York metropolitan area as an epicenter of this pandemic beginning in March 2020, a consortium of laboratory leaders from the assembled New York academic medical institutions was formed to help identify and solve the challenges of deploying testing. This report brings forward the experience of this consortium, based on the real-world challenges which we encountered in testing patients and in supporting the recovery effort to reestablish the health care workplace. In coordination with the Greater New York Hospital Association and with the public health laboratory of New York State, this consortium communicated with state leadership to help inform public decision-making addressing the crisis. Throu...
Diagnostic Pathology, 2020
Background Multiplex immunohistochemistry (mIHC) permits the labeling of six or more distinct cel... more Background Multiplex immunohistochemistry (mIHC) permits the labeling of six or more distinct cell types within a single histologic tissue section. The classification of each cell type requires detection of uniquely colored chromogens localized to cells expressing biomarkers of interest. The most comprehensive and reproducible method to evaluate such slides is to employ digital pathology and image analysis pipelines to whole-slide images (WSIs). Our suite of deep learning tools quantitatively evaluates the expression of six biomarkers in mIHC WSIs. These methods address the current lack of readily available methods to evaluate more than four biomarkers and circumvent the need for specialized instrumentation to spectrally separate different colors. The use case application for our methods is a study that investigates tumor immune interactions in pancreatic ductal adenocarcinoma (PDAC) with a customized mIHC panel. Methods Six different colored chromogens were utilized to label T-cell...
Mucosal Immunology, 2020
Interleukin-22 (IL-22) signaling in the intestines is critical for promoting tissue-protective fu... more Interleukin-22 (IL-22) signaling in the intestines is critical for promoting tissue-protective functions. However, since a diverse array of cell types (absorptive and secretory epithelium as well as stem cells) express IL-22Ra1, a receptor for IL-22, it has been difficult to determine what cell type(s) specifically respond to IL-22 to mediate intestinal mucosal host defense. Here, we report that IL-22 signaling in the small intestine is positively correlated with Paneth cell differentiation programs. Our Il22Ra1fl/fl;Lgr5-EGFP-creERT2-specific knockout mice and, independently, our lineage-tracing findings rule out the involvement of Lgr5+ intestinal stem cell (ISC)-dependent IL-22Ra1 signaling in regulating the lineage commitment of epithelial cells, including Paneth cells. Using novel Paneth cell-specific IL-22Ra1 knockout mice (Il22Ra1fl/fl;Defa6-cre), we show that IL-22 signaling in Paneth cells is required for small intestinal host defense. We show that Paneth cell maturation, a...
Diagnostic Pathology, 2020
An amendment to this paper has been published and can be accessed via the original article.
British Journal of Cancer, 2020