Expression of P53, P27 and KI‐67 in colorectal cancer patients of various ethnic origins: Clinical and tissue microarray based analysis

Cohen, Tzeela; Prus, Diana; Shia, Jinru; Abu-Wasel, Bassam; Pinto, Meir G; Freund, Herbert R.; Stojadinovic, Alexander; Grakov, Anna; Peretz, Tamar; Nissan, Aviram

doi:10.1002/jso.20989

Cited by 11 publications

(3 citation statements)

References 44 publications

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“…We also found that dMMR/MSI-H was not associated with Ki-67 expression, which is in keeping with the view that the expression of Ki-67 did not correlate with CRC biological behavior and prognosis. 48,49 Additionally, our data also showed that MSI-H was significantly associated with TNM stage II. Several studies demonstrated that 5-FU-based adjuvant chemotherapy not only was invalid but it might also have a detrimental impact on survival in stage II MSI-H CRC patients.…”

Section: Discussionsupporting

confidence: 68%

<p>Evaluation of Concordance Between Deficient Mismatch Repair and Microsatellite Instability Testing and Their Association with Clinicopathological Features in Colorectal Cancer</p>

Bai¹,

Wang²,

Cheng³

et al. 2020

CMAR

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Background: Microsatellite instability (MSI) is one of the most important molecular characteristics of colorectal cancer (CRC), which mainly results from defective DNA mismatch repair (MMR). This study was performed to investigate the concordance between deficient MMR and MSI testing, and to evaluate the association of these two results with clinicopathological characteristics in Chinese CRC patients. Methods: A total of 738 CRC patients were included. Tumor tissues and paired peripheral blood specimens were obtained. Screening for MMR was investigated using immunohistochemical (IHC) technique, and multiple polymerase chain reaction-capillary electrophoresis (PCR-CE) method was performed to detect the MSI status. All clinicopathological data, immunohistochemistry and microsatellite instability analyses were then statistically analyzed. Results: Of the 738 (17.75%) CRC patients, 131 expressed as deficient mismatch repair (dMMR) status, and postmeiotic segregation increased 2 (PMS2) deficiency was the most frequent deficiency among these four MMR proteins. MSI-high (MSI-H) status occurred in 74 of the 738 (10.03%) CRC patients, 55 of whom showed instability at all six mononucleotides repeat markers. dMMR was significantly associated with MSI-H and moderate concordance was observed between IHC and PCR-CE in evaluating deficient MMR/MSI through Kappa test. Statistically, dMMR was significantly associated with younger age, right-sided colon and poor differentiation. MSI-H was associated with younger age, rightsided colon, poor differentiation, mucinous type and tumor, node, metastasis (TNM) stage II. Conclusion: A moderate concordance between deficient MMR and MSI testing indicates that both IHC and PCR-CE methods should be routinely tested to provide reliable data for clinical treatment decisions.

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Section: Discussionsupporting

confidence: 68%

<p>Evaluation of Concordance Between Deficient Mismatch Repair and Microsatellite Instability Testing and Their Association with Clinicopathological Features in Colorectal Cancer</p>

Bai¹,

Wang²,

Cheng³

et al. 2020

CMAR

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“…TMA blocks were cut to 5-µm sections and deparaffinized, rehydrated in graded alcohol, and processed. 17 Antibodies were used to recognize CD3 (F7.2.38, Dako, Carpinteria, CA), CD8 (c8/144B, Dako), CD4 (polyclonal goat, R&D Systems, Minneapolis, MN), and FoxP3 (236A/E7, Abcam Inc., Cambridge, MA). Biotinylated secondary immunoglobulins were added (Vector Laboratories, Inc., Burlingame, CA) followed by avidinbiotin peroxidase complexes (1:25; Vector Laboratories, Inc.).…”

Section: Methodsmentioning

confidence: 99%

Regulatory T Cell Infiltration Predicts Outcome Following Resection of Colorectal Cancer Liver Metastases

et al. 2012

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Background Tumor-infiltrating lymphocyte (TIL) counts in colorectal cancer liver metastases (CRCLM) predict survival following resection. While CD4 and CD8 T cells have been correlated with outcome following CRCLM resection, the role of regulatory T cells (Treg) is not well defined. Methods TIL in 188 patients who underwent CRCLM resection between 1998 and 2000 were analyzed by immunohistochemistry using tissue microarrays. Correlation between TIL composition and outcome was determined while controlling for established prognostic factors. Total T cells (CD3), helper T cells (CD4), cytotoxic T cells (CD8), and Treg (FoxP3) were analyzed. Results Median follow-up time was 40 months for all patients and 95 months for survivors. Overall survival (OS) at 5 and 10 years was 40 and 25 %, respectively. The CD4 T cell count correlated with OS (p = .02) and recurrencefree survival (p = .04). A high number of CD8 T cells relative to total T cells (CD8:CD3 ratio) predicted longer OS times (p = .05). Analysis of Treg revealed that high FoxP3:CD4 (p = .03) and FoxP3:CD8 (p = .05) ratios were independent predictors of shorter OS. Patients with a high clinical risk score (CRS) were more likely to have a high number of intratumoral Treg, and patients ≥65 years old had a less robust CRCLM T cell infiltration. Conclusions A high number of Treg relative to CD4 or CD8 T cells predicted poor outcome, suggesting an immunosuppressive role for FoxP3 + TIL. The intratumoral immune response was an independent predictor of outcome in patients with colorectal liver metastases.

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“…After review of the archived primary tumour haematoxylin and eosin (H&E) slides and diagnostic confirmation, sections were deparaffinized, rehydrated in graded alcohol, and processed as previously described 23 . Monoclonal antibodies were used to detect CD3 (F7.2.38; Dako North America, Inc., Carpinteria, CA, USA), CD8 (c8/144B; Dako North America, Inc.), FoxP3 (236A/E7; Abcam, Inc., Cambridge, MA, USA) and CD4 (polyclonal goat; R&D Systems, Inc., Minneapolis, MN, USA).…”

Section: Methodsmentioning

confidence: 99%

T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases

Katz

Donkor

Glasgow

et al. 2010

HPB

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Expression of P53, P27 and KI‐67 in colorectal cancer patients of various ethnic origins: Clinical and tissue microarray based analysis

Abstract: Ethnicity among Ashkenazi and SJ and PA appears to have a significant impact on disease outcome in patients with CRC patients, while primary tumor expression of p53, p27 and Ki-67 was unrelated to disease outcome.

Cited by 11 publications

References 44 publications

<p>Evaluation of Concordance Between Deficient Mismatch Repair and Microsatellite Instability Testing and Their Association with Clinicopathological Features in Colorectal Cancer</p>

<p>Evaluation of Concordance Between Deficient Mismatch Repair and Microsatellite Instability Testing and Their Association with Clinicopathological Features in Colorectal Cancer</p>

Regulatory T Cell Infiltration Predicts Outcome Following Resection of Colorectal Cancer Liver Metastases

T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases

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