title: Signet ring cell carcinoma of the colorectum: correlations between microsatellite instability, clinicopathologic features and survival.
abstract: Colorectal cancer with microsatellite instability has a characteristic clinicopathologic profile, featuring right-sided, lymphocyte-rich tumors with a better prognosis than microsatellite stable (MSS) carcinoma. Mucinous and signet ring cell carcinomas are both over-represented among microsatellite instability-high cancers. The clinicopathologic features of mucinous microsatellite instability-high cancer parallel those of the overall microsatellite instability-high set, but it is not known whether the same is true for signet ring cell carcinoma, particularly given the fact that signet ring histology is a well-documented adverse prognostic factor. We recorded age, sex, tumor size, site, grade, stage, histologic pattern, growth pattern, Crohn-like reaction, vascular invasion and tumor-infiltrating lymphocytes in 72 resected signet ring cell carcinomas of the colorectum. Microsatellite instability was determined by a combination of polymerase chain reaction and immunohistochemical stains for hMLH1, hMSH2 and hMSH6. Tumors with instability at >30% of informative markers and/or loss of hMLH1 or hMSH2 expression were designated microsatellite instability-high; all others were classified as MSS. A total of 22 (31%) signet ring cell carcinomas were microsatellite instability-high. Compared to MSS signet ring cell carcinoma, they were more likely to be right-sided (81 vs 45%, P=0.005) and to affect older patients (68 vs 26%, P=0.0007) of female sex (59 vs 28%, P=0.03). Crohn-like reaction (45 vs 16%, P=0.02) and high tumor infiltrating lymphocyte counts (32 vs 8%, P=0.03) were more common in the microsatellite instability-high setting. There was no significant difference in 5-year survival in microsatellite instability-high vs MSS patients (41 vs 34%, P=0.3). In conclusion, approximately one-third of signet ring carcinomas of the colorectum are microsatellite instability-high. Microsatellite instability-high signet ring carcinomas share clinicopathologic features with other microsatellite instability-high cancers: older age group, female preponderance, right-sided location, Crohn-like reaction and numerous tumor-infiltrating lymphocytes. Microsatellite instability status does not appear to be a significant predictor of survival in signet ring cell carcinoma of the colorectum.
authors.affiliation: Department of Pathology, University of California San Francisco, Veteran Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kakar
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein