Sonali Susmita Nayak1, Paromita Roy1, Neeraj Arora2, Indu Arun1, Manas Kumar Roy3, Sudeep Banerjee3, Indranil Mallick4, Mohandas K Mallath5. 1. Department of Pathology, Tata Medical Centre, Kolkata, West Bengal, India. 2. Department of Laboratory Medicine and Molecular Genetics, Tata Medical Centre, Kolkata, West Bengal, India. 3. Department of Surgical Oncology, Tata Medical Centre, Kolkata, West Bengal, India. 4. Department of Radiation Oncology, Tata Medical Center, Kolkata, West Bengal, India. 5. Department of GI Medicine, Tata Medical Center, Kolkata, West Bengal, India.
Abstract
AIM: Microsatellite instability (MSI) pathway is known to be implicated in carcinogenesis of 15% colorectal carcinomas (CRC), including 2%-3% of cases of Lynch syndrome, as per western literature. MSI status has important prognostic and therapeutic implications. The prevalence of MSI in Indian CRC patients is unknown. We aimed to determine the prevalence by studying 231 consecutive unselected cases of CRC. METHODS: Tissue microarrays using duplicate cores per case for 141 cases, and whole tissue sections for 90 cases, were used. Immunohistochemistry with four mismatch repair (MMR) markers - MLH1, MSH2, MSH6, and PMS2 was performed. Molecular analysis for MSI status was performed in 18 randomly selected cases. Correlation with various clinical and histopathological features was done using univariate and multivariate analysis. RESULTS: Loss of MMR immunohistochemical (IHC) was seen in 53/231 cases, i.e. 22.94% (95% confidence interval 17.52%-28.36%). MLH1-PMS2 dual loss comprised 13.9%, MSH2-MSH6 7.4%, and isolated PMS2 loss in 1.73% of cases. Univariate analysis showed significant association with age (<60 years), right-sided tumor location, histologic type, high grade, the presence of severe intratumoral lymphocytic (ITL) and peri-tumoral lymphocytic response, and N0 nodal stage. On multivariate analysis, independent variables were age < 60 years, right-sided location, and severe ITL. Molecular testing for MSI corroborated with the IHC results. CONCLUSION: The study results show a slightly higher prevalence of MSI-H phenotype, compared to Western literature, stressing the need for more widespread testing for better clinical management and identification of possible hereditary colon cancer syndrome.
AIM: Microsatellite instability (MSI) pathway is known to be implicated in carcinogenesis of 15% colorectal carcinomas (CRC), including 2%-3% of cases of Lynch syndrome, as per western literature. MSI status has important prognostic and therapeutic implications. The prevalence of MSI in Indian CRC patients is unknown. We aimed to determine the prevalence by studying 231 consecutive unselected cases of CRC. METHODS: Tissue microarrays using duplicate cores per case for 141 cases, and whole tissue sections for 90 cases, were used. Immunohistochemistry with four mismatch repair (MMR) markers - MLH1, MSH2, MSH6, and PMS2 was performed. Molecular analysis for MSI status was performed in 18 randomly selected cases. Correlation with various clinical and histopathological features was done using univariate and multivariate analysis. RESULTS: Loss of MMR immunohistochemical (IHC) was seen in 53/231 cases, i.e. 22.94% (95% confidence interval 17.52%-28.36%). MLH1-PMS2 dual loss comprised 13.9%, MSH2-MSH6 7.4%, and isolated PMS2 loss in 1.73% of cases. Univariate analysis showed significant association with age (<60 years), right-sided tumor location, histologic type, high grade, the presence of severe intratumoral lymphocytic (ITL) and peri-tumoral lymphocytic response, and N0 nodal stage. On multivariate analysis, independent variables were age < 60 years, right-sided location, and severe ITL. Molecular testing for MSI corroborated with the IHC results. CONCLUSION: The study results show a slightly higher prevalence of MSI-H phenotype, compared to Western literature, stressing the need for more widespread testing for better clinical management and identification of possible hereditary colon cancer syndrome.
Entities:
Keywords:
Colorectal carcinoma; microsatellite instability; mismatch repair protein
Authors: Lia Head; Katja Kiseljak-Vassiliades; Toshimasa J Clark; Hilary Somerset; Jonathan King; Christopher Raeburn; Maria Albuja-Cruz; Michael Weyant; Joseph Cleveland; Margaret E Wierman; Stephen Leong Journal: J Endocr Soc Date: 2019-10-11
Authors: Ryan J Slovak; Hong-Jai Park; William M Kamp; Johannes M Ludwig; Insoo Kang; Hyun S Kim Journal: Sci Rep Date: 2021-03-26 Impact factor: 4.379
Authors: David Dum; Stefan Steurer; Ronald Simon; Pia Victoria Zimmermann; Eike Burandt; Till Sebastian Clauditz; Margit Fisch; Michael Rink; Roland Dahlem; Wolfgang Höppner; Henrik Zecha; Ousman Doh; Cord Matthies; Waldemar Wilczak; Guido Sauter; Christoph Fraune Journal: Transl Androl Urol Date: 2021-03