KRAS mutations analysis in mucinous epithelial lesions of the endometrium / 中华病理学杂志

Objective@#To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features.@*Methods@#The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups.@*Results@#The patients′age ranged from 33 to 77 years [mean (55.12±9.34) years, median 55 years]. None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and 8/9 in mucinous carcinoma (MC), respectively. The differences were statistically significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05).@*Conclusion@#The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.

Analysis of the relationship of DNA mismatch repair with clinicopathologic features and prognosis of colon cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the relationship between DNA mismatch repair (MMR) and clinicopathologic features and prognosis in patients with stages II and III colon cancers.</p><p><b>METHODS</b>The clinical and pathological data of 440 patients with stage II/III colon cancer after radical resection were retrospectively reviewed and analyzed. Immunohistochemical staining was used to assess the expression of MMR proteins (MLH1, MSH2, MSH6 and PMS2), and the correlation between DNA MMR and clinicopathological features and prognosis of colon cancers was analyzed.</p><p><b>RESULTS</b>Of the 440 tumor samples tested for DNA mismatch repair status, 90 (20.5%) demonstrated defective DNA mismatch repair and 350 (79.5%) had proficient DNA mismatch repair. Defective DNA mismatch repair (dMMR) was associated with young patients (≤ 60), proximal colon cancer, stage II, poorly differentiated adenocarcinoma and mucinous adenocarcinoma (P<0.05 for all). Among the 440 patients, 126 (28.6%) cases had recurrence or metastasis and 93 (21.1%) died during the median follow-up of 61.0 months. The five-year disease-free survival (DFS) rate was 82.2% among the patients with tumor exhibiting dMMR, significantly higher than that in patients with tumors exhibiting pMMR (68.9%, P=0.02). The univariate and mutlivariate analyses showed that the MMR status is an independent factor affecting 5-year disease-free survival and overall survival (OS) in colon cancer patients (P<0.05 for both).</p><p><b>CONCLUSIONS</b>Defective DNA mismatch repair (dMMR) is associated with patients with proximal colon cancer, stage II and poorly defferentiated adenocarcinoma and mucinous adenocarcinoma. The prognosis for patients with dMMR is better than those with pMMR. dMMR may be a useful biomarker for the prognosis of colon cancer.</p>

Correlations between DNA mismatch repair (MMR) and prognosis and prediction of treatment efficacy in stage II/II colon cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the role of DNA mismatch repair (MMR) as a prognostic indicator of radical resection and a predictor of fluorouracil-based adjuvant therapy benefit in patients with stage II/III colon cancer.</p><p><b>METHODS</b>The clinicopathological characteristics of 172 patients with stage II/III colon cancer who underwent radical resection were retrospectively analyzed. Immunohistochemical staining was used to detect the expression of DNA mismatch repair (MLH1/MSH2/MSH6/PMS2) in the tumor tissues.</p><p><b>RESULTS</b>Among a total of 172 patients, there were 38 (22.1%) cases with defective DNA mismatch repair (dMMR) and 134 (77.9%) cases with proficient DNA mismatch repair (pMMR). Among the 115 patients who did not receive adjuvant chemotherapy, those with tumor displaying dMMR had a better 5-year overall survival (OS) rate and disease-free survival (DFS) rate than the patients with proficient DNA mismatch repair (pMMR) (88.0% vs. 66.7%, P = 0.040; 84.0% vs. 60.0%, P = 0.034). The benefit of adjuvant chemotherapy differed significantly according to the MMR status. Adjuvant 5-Fu chemotherapy improved the 5-year overall survival rate among 134 patients with pMMR (86.4%) than that in patients treated by surgery alone (66.7%, P = 0.012). By contrast, there was no benefit of adjuvant 5-Fu chemotherapy in the patients with dMMR (61.5% vs. 86.4%, P = 0.062), which was even more clear the 5-year disease-free survival rate (53.8% vs. 84.0%, P = 0.038).</p><p><b>CONCLUSIONS</b>MMR status is a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II/III colon cancer. Patients with stage II/III colon cancer displaying dMMR have a better prognosis than those with pMMR.</p>

Significance of microsatellite instability in colorectal cancer / 国际肿瘤学杂志

Microsatellite instability (MSI) is an important molecular mechanism in colorectal cancer's initiation and progression,which has significant clinical significance.MSI is a diagnostic biomarker for Lynch synchrome.Moreover,the clinical implication of MSI testing extends to the role of prognostic marker and predictive maker,due to the better outcome of patients with MSI positive colorectal cancer and a general lack of response to chemotherapy employing 5-fluorouracil.