Analysis of the Clinicopathological Characteristics of Stage I–III Colorectal Cancer Patients Deficient in Mismatch Repair Proteins

Yue, Liang; Cai, Xinling; Xu, Zheng; Yin, Han

doi:10.2147/ott.s278029

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…Therefore, patients with early dMMR CRCs have a relatively better prognosis than pMMR patients in the same period. These data are roughly like the current research results of other scholars [ 23 , 24 ].…”

Section: Discussionsupporting

confidence: 91%

Analysis of clinical characteristics of mismatch repair status in colorectal cancer: a multicenter retrospective study

Mao,

He,

Chu

et al. 2024

Int J Colorectal Dis

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Background Microsatellite instability (MSI) caused by DNA mismatch repair (MMR) deficiency is of great significance in the occurrence, diagnosis and treatment of colorectal cancer (CRC). Aim This study aimed to analyze the relationship between mismatch repair status and clinical characteristics of CRC. Methods The histopathological results and clinical characteristics of 2029 patients who suffered from CRC and underwent surgery at two centers from 2018 to 2020 were determined. After screening the importance of clinical characteristics through machine learning algorithms, the patients were divided into deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR) groups based on the immunohistochemistry results and the clinical feature data between the two groups were observed by statistical methods. Results The dMMR and pMMR groups had significant differences in histologic type, TNM stage, maximum tumor diameter, lymph node metastasis, differentiation grade, gross appearance, and vascular invasion. There were significant differences between the MLH1 groups in age, histologic type, TNM stage, lymph node metastasis, tumor location, and depth of invasion. The MSH2 groups were significantly different in age. The MSH6 groups had significant differences in age, histologic type, and TNM stage. There were significant differences between the PMS2 groups in lymph node metastasis and tumor location. CRC was dominated by MLH1 and PMS2 combined expression loss (41.77%). There was a positive correlation between MLH1 and MSH2 and between MSH6 and PMS2 as well. Conclusions The proportion of mucinous adenocarcinoma, protruding type, and poor differentiation is relatively high in dMMR CRCs, but lymph node metastasis is rare. It is worth noting that the expression of MMR protein has different prognostic significance in different stages of CRC disease.

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Section: Discussionsupporting

confidence: 91%

Analysis of clinical characteristics of mismatch repair status in colorectal cancer: a multicenter retrospective study

Mao,

He,

Chu

et al. 2024

Int J Colorectal Dis

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“…We also found a significant association of dMMR CRC with T4 stage, higher tumor grade, and mucinous differentiation, however, the association of dMMR CRC with younger age was not established in our study. Similarly, Liang et al [ 12 ] did not find any association of dMMR status with LVI, as noted in our study. Sacdalan et al [ 13 ] also reported aggressive histological features (poor differentiation, mucinous histology) of dMMR CRC in Filipino patients.…”

Section: Discussionsupporting

confidence: 89%

“…They found a significant association of dMMR status with age, gender, and tumor site, whereas no significant association was noted with T- and N-stages [ 11 ]. Conversely, Liang et al [ 12 ] in a study including 61 CRC patients concluded that there was a significant association of dMMR status with age (<55 years), female gender, location (right colon), tumor size (>5 cm), T-stage (T4), high grade, and mucinous differentiation. We also found a significant association of dMMR CRC with T4 stage, higher tumor grade, and mucinous differentiation, however, the association of dMMR CRC with younger age was not established in our study.…”

Section: Discussionmentioning

confidence: 99%

Mismatch Repair Deficient (dMMR) Colorectal Carcinoma in a Pakistani Cohort: Association With Clinical and Pathological Parameters

Hashmi,

Bukhari,

Rizwan

et al. 2023

Cureus

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Introduction Microsatellite instability (MSI) is an important pathway in colorectal carcinoma (CRC) pathogenesis. MSI occurs due to mutations in mismatch repair (MMR) genes that include MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). CRC with MSI is termed MMR deficient (dMMR) CRC. Conversely, CRC with intact MMR genes is called microsatellite stable (MSS) or MMR proficient (pMMR). In this study, we compared the clinicopathological features of dMMR CRC with pMMR CRC. Methods It was a retrospective study conducted in the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, from March 2020 to February 2022, over a duration of two years. Biopsy-proven cases of CRC with upfront surgical resection were included in the study. Microscopic examination was performed to evaluate tumor type, grade, and extent of invasion, presence of necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), peritumoral lymphocytes (PTL), intratumoral lymphocytes (ITL), and nodal metastasis. Immunohistochemical staining was performed using antibodies, namely, MLH1, PMS2, MSH2, and MSH6. Any loss of nuclear expression in tumor cells was termed dMMR or microsatellite instable, whereas the intact nuclear expression in tumor cells was labeled as MSS or pMMR. Results A total of 135 cases of CRC were included in the study. The mean age at diagnosis was 46.76 ± 17.74 years, with female predominance (60.7%). The loss of MLH1, PMS2, MSH2, and MSH6 expression was noted in 39.3%, 34.1%, 17.8%, and 16.3% cases, respectively. Overall, 59.3% of CRCs were pMMR, while 40.7% were dMMR. A significant association of MMR status was noted with respect to age, PNI, LVI, tumor grade, tumor (T) and nodal (N) stage, mucinous differentiation, and ITL. dMMR CRC was significantly above 50 years than pMMR CRC. The frequency of PNI and LVI was lower in dMMR CRC than in pMMR CRC. Conversely, the higher grade (grade 3) and higher T-stage (T4) were associated with dMMR CRC. Alternatively, the frequency of higher N stage (N2b) was more commonly seen in pMMR CRC. Moreover, mucinous differentiation and ITL were significantly associated with dMMR CRC. Conclusion A significant proportion of CRC patients in our population demonstrated dMMR status. dMMR CRC had a higher histological grade with a higher frequency of mucinous differentiation and higher T-stage. Conversely, the presence of LVI, PNI, and higher N stages were associated with pMMR CRC.

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“… 39 Besides, CRCs with a higher rate of faulty mismatch repair (MMR) mechanisms have been reported to be associated with larger tumor diameter. 40 Since the mutations in the MSH3 gene, 1 of the 7 MMR genes in humans, has been suggested to play a role in tumor progression in CRCs, studies on this subject have reported that loss of MSH3 expression was associated with lymph node metastasis and distant metastasis in CRCs. 41 Our study revealed a significant association between the MSH3 mutation, for the prognostic value of which no consensus has yet been reached, and tumor diameter in CRCs.…”

Section: Discussionmentioning

confidence: 99%

Mutation Profile via Next-Generation Sequencing in Patients with Colorectal Adenocarcinoma and Its Clinicopathological Correlation

Osman,

Kahraman Cetin,

Erdogdu

et al. 2023

Turkish Journal of Gastroenterology

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Background/Aims: Recent studies that reveal the molecular profiles of colorectal carcinomas have demonstrated tumor heterogeneity. Characterization of colorectal carcinoma-specific genomic alterations is essential for developing more successful and targeted treatment protocols. Moreover, it is vital in elucidating the pathogenesis and mechanisms of resistance against treatment and predicting prognosis. Materials and Methods: The study included 73 cases diagnosed with colorectal carcinomas and subjected to molecular analysis by the next-generation sequencing. The association between the clinicopathologic parameters and pathogenic mutations detected in 32 genes was evaluated. Results: Pathogenic mutations were determined in a total of 24 genes. The Cell Division Cycle 27 (CDC27), Kirsten rat sarcoma viral proto-oncogene (KRAS), serine/threonine protein kinase B-raf (BRAF), phosphatase and tensin homolog, breast cancer 2 (BRCA2), and phosphotidylinositol-4,5-biphosphate 3-kinase (PIK3CA) mutations were determined at higher rates, with the adenomatous polyposis coli mutation determined at a lower rate than in the literature. There were significant positive correlations between CDC27 and phosphatase and tensin homolog (PTEN), PTEN and BRCA2, and PTEN and adenomatous polyposis coli (APC) concomitant mutations, whereas negative correlations were present between BRAF and KRAS. Statistically significant relationships were present between KRAS exon 2 and mucinous morphology, PIK3CA and absence of perineural invasion, BRAF and tumor differentiation/localization, MutS homolog 3 (MSH3) and tumor diameter, and BRCA2 and absence of lymph node metastasis. Conclusion: It is necessary to have a comprehensive database of genomic alterations of colorectal carcinomas to interpret mutations more accurately clinically. There are no studies on the frequency of mutations in colorectal carcinomas in the Turkish population; thus, follow-up and treatment protocols are organized following the European and American databases and guidelines. A comprehensive study of the colorectal carcinoma patients’ mutation profile in the Turkish patient cohort by the next-generation sequencing method will help to provide significant therapeutic, prognostic, and predictive data and design more successful treatment and follow-up strategies.

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Analysis of the Clinicopathological Characteristics of Stage I–III Colorectal Cancer Patients Deficient in Mismatch Repair Proteins

Cited by 9 publications

References 36 publications

Analysis of clinical characteristics of mismatch repair status in colorectal cancer: a multicenter retrospective study

Analysis of clinical characteristics of mismatch repair status in colorectal cancer: a multicenter retrospective study

Mismatch Repair Deficient (dMMR) Colorectal Carcinoma in a Pakistani Cohort: Association With Clinical and Pathological Parameters

Mutation Profile via Next-Generation Sequencing in Patients with Colorectal Adenocarcinoma and Its Clinicopathological Correlation

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