Predictive Value of Tumor Proliferative Indices in Periampullary Cancers: Ki‐67, Mitotic Activity Index (MI) and Volume Corrected Mitotic Index (M/V) Using Tissue Microarrays

Aloysius, Mark M.; Hewavisenthi, S.J.de S.; Bates, Timothy E.; Lobo, Dileep N.; Zaitoun, Abed M.

doi:10.1007/s00268-010-0681-3

Cited by 9 publications

(5 citation statements)

References 43 publications

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“…Additionally, in iCCA, we performed a correlation analysis between the syndecan-1 H-score and the residual tumor classification, the lymph node status, the iCCA subclassification (small and large duct type), and the Ki-67 proliferation rate. As expected, the proliferation rate correlated with histological tumor grade [23]. No statistically significant association between the H-score and the prognostically important marker proliferation rate, residual tumor status, lymph node status, and histological subtype analysis was detected (Ki-67: ρ = 0.08 (p = 0.925), R-status: ρ = 0.062 (p = 0.484), iCCA subclassification ρ = 0.002 (p = 0.985).…”

Section: Discussionsupporting

confidence: 81%

Clinicopathological Significance of Syndecan-1 in Cholangiocarcinoma: A Study Based on Immunohistochemistry and Public Sequencing Data

Gerber

Bartsch

Wagner

et al. 2021

JCM

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Background: Syndecan-1 (CD138; SDC1) is a heparan sulfate proteoglycan that has been attributed a key role in cancer progression in ductal adenocarcinoma of the pancreas. We therefore aimed to investigate the role of syndecan-1 in cholangiocarcinoma. Methods: We analyzed syndecan-1 expression in a large, clinicopathologically well-characterized collective of 154 intrahepatic cholangiocarcinoma, 221 extrahepatic cholangiocarcinomas, and 95 gallbladder carcinomas as well as respective normal tissues and precursor lesions by immunohistochemistry with digital image analysis and correlated with recurrence-free survival and prognostic markers. Furthermore, we conducted an analysis of cancer genes in the cholangiocarcinoma cohort of The Cancer Genome Atlas (TCGA). Results: During cholangiocarcinogenesis, syndecan-1-expression decreased when compared to normal bile ducts and biliary intraepithelial neoplasia; however, syndecan-1 levels were found to be elevated in lymph node metastases. In the TCGA cohort, high mRNA SDC1 levels were associated with poor prognosis in intrahepatic cholangiocarcinoma. However, in our large cohort, the immunohistochemical syndecan-1 expression did not significantly correlate with recurrence-free survival. Conclusions: Syndecan-1 was found to be downregulated during cholangiocarcinogenesis, yet we could not show significant effects on prognosis on protein level. Further analyses are needed to further depict its specific role.

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Section: Discussionsupporting

confidence: 81%

Clinicopathological Significance of Syndecan-1 in Cholangiocarcinoma: A Study Based on Immunohistochemistry and Public Sequencing Data

Gerber

Bartsch

Wagner

et al. 2021

JCM

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“…One study has shown that lower levels of Ki-67 were associated with a better outcome in pancreatic cancer patients (37), although other studies did not find an association (38,39). The predictive value of Ki-67 was reinforced by recent studies that showed better survival or decreased tumor volume with lower levels of Ki-67 (40,41). We further confirmed the anti-proliferative effect of PEITC by PCNA staining which has been reported to correlate positively with the histological grade of pancreatic cancer (42).…”

Section: Discussionmentioning

confidence: 98%

Phenethyl Isothiocyanate Inhibits Proliferation and Induces Apoptosis in Pancreatic Cancer CellsIn Vitroand in a MIAPaca2 Xenograft Animal Model

Stan

Singh

Whitcomb

et al. 2013

Nutrition and Cancer

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Pancreatic cancer is often diagnosed at an advanced stage and it has a poor prognosis which points to an increased need to develop effective chemoprevention strategies for this disease. We examined the ability of phenethyl isothiocyanate (PEITC), a naturally-occurring isothiocyanate found in cruciferous vegetables, to inhibit the growth of pancreatic cancer cells in vitro and in a MIAPaca2 xenograft animal model. Exposure to PEITC inhibited pancreatic cancer cell growth in a dose-dependent manner, with an IC50 of approximately 7 μmol/L. PEITC treatment induced G2/M phase cell cycle arrest, down-regulated the anti-apoptotic proteins Bcl-2 and Bcl-XL, up-regulated the pro-apoptotic protein Bak, and suppressed Notch 1 and 2 levels. In addition, treatment with PEITC induced cleavage of poly-(ADP-ribose) polymerase and led to increased cytoplasmic histone-associated DNA fragmentation and subdiploid (apoptotic) fraction in pancreatic cancer cells. Oral administration of PEITC suppressed the growth of pancreatic cancer cells in a MIAPaca2 xenograft animal model. Our data show that PEITC exerts its inhibitory effect on pancreatic cancer cells through several mechanisms including G2/M phase cell cycle arrest and induction of apoptosis, and support further investigation of PEITC as a chemopreventive agent for pancreatic cancer.

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“…The proportion of tumour and stroma was estimated visually by both researchers independently. From these figures, the densities of lymphocytes per mm 2 were calculated using the TMA core area as reference [20]. The mean area of TMA cores was 0.355 mm 2 .…”

Section: Methodsmentioning

confidence: 99%

The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays

et al. 2013

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BackgroundTumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma.MethodsAfter histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high’ and 'low’ for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features.ResultsCD3 and CD8 positive lymphocytes were associated with grade of tumour differentiation. The presence of intratumoural CD3 positive cells was associated with improved survival (p = 0.028), and intratumoural and stromal CD3 in combination also correlated with improved survival (p = 0.043). When CD20 positive lymphocyte levels were high, survival improved (p = 0.029) and similar results were seen for CD20 in combination with intratumoural CD3 (p = 0.001) and stromal CD8 (p = 0.013).ConclusionsThis study has shown a correlation between the presence of TALs and survival in pancreatic ductal adenocarcinoma.

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Predictive Value of Tumor Proliferative Indices in Periampullary Cancers: Ki‐67, Mitotic Activity Index (MI) and Volume Corrected Mitotic Index (M/V) Using Tissue Microarrays

Abstract: In periampullary cancers, Ki-67 and MI are proliferative indices predictive of tumor behavior. M/V was predictive of survival in tumors of the pancreaticobiliary subtype.

Cited by 9 publications

References 43 publications

Clinicopathological Significance of Syndecan-1 in Cholangiocarcinoma: A Study Based on Immunohistochemistry and Public Sequencing Data

Clinicopathological Significance of Syndecan-1 in Cholangiocarcinoma: A Study Based on Immunohistochemistry and Public Sequencing Data

Phenethyl Isothiocyanate Inhibits Proliferation and Induces Apoptosis in Pancreatic Cancer CellsIn Vitroand in a MIAPaca2 Xenograft Animal Model

The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays

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