Medullary-Type Poorly Differentiated Adenocarcinoma of the Large Bowel: A Distinct Clinicopathologic Entity Characterized by Microsatellite Instability and Improved Survival

Abstract

All these data strongly indicate that MTAs represent a distinct pathologic entity, with specific histologic appearance and peculiar clinical and genetic features. These tumors need to be classified separately from other poorly differentiated colorectal carcinomas.

Hypermethylation of the hMLH1 promoter with absent hMLH1 expression in medullary-type poorly differentiated colorectal adenocarcinoma in the elderly

“…This result is in accord with that of other investigators. 4,10,14 Although the high incidence of absent hMLH1 expression was reported in poorly differentiated colorectal adenocarcinomas, 14 our results indicated that in poorly differentiated adenocarcinoma, the medullary-type carcinoma is primarily affected as compared with pleomorphictype carcinoma. In view of the histopathological type of tumor, we are the first to describe hypermethylation of the hMLH1 promoter in medullarytype carcinomas.…”

“…21,31 These facts may contribute to the observation that medullary-type carcinomas occur more frequently in the older female patient and in the proximal colon. 6,10 The present study has suggested that medullarytype poorly differentiated carcinomas should be distinguished from other adenocarcinomas with minimal or no glandular differentiation due to its biological behavior. Since approximately 90% of medullary-type carcinomas showed an absence of hMLH1 protein expression together with microsatellite instability, immunohistochemistry for the detection of hMLH1 protein may be useful in predicting the tumor type.…”

“…[1][2][3] Poorly differentiated lesions are heterogeneous with respect to their clinicopathologic and molecular features. [4][5][6][7][8] A peculiar type of poorly differentiated colorectal adenocarcinoma has been recently recognized and termed either medullary-type poorly differentiated adenocarcinoma, 4,6,9,10 solid-type poorly differentiated adenocarcinoma, 5 or large cell minimally differentiated carcinoma. 11 Histologically, the tumor is characterized by a small uniform population of tumor cells with fine chromatin and prominent nucleoli.…”

“…The main clinicopathologic features of the tumor are its predominant occurrence in elderly women, a location of the proximal colon, and a relatively favorable prognosis in spite of the highgrade histological features. 4,6,10 Furthermore, recent molecular studies demonstrate that medullary-type carcinomas show a diploid DNA pattern, a high frequency of microsatellite instability, and low p53 expression. 4,10 Cancers with high levels of microsatellite instability are the hallmark of hereditary nonpolyposis colorectal cancer, and microsatellite instability occurs in 10-15% of sporadic colorectal carcinomas.…”

“…4,6,10 Furthermore, recent molecular studies demonstrate that medullary-type carcinomas show a diploid DNA pattern, a high frequency of microsatellite instability, and low p53 expression. 4,10 Cancers with high levels of microsatellite instability are the hallmark of hereditary nonpolyposis colorectal cancer, and microsatellite instability occurs in 10-15% of sporadic colorectal carcinomas. Colorectal adenocarcinomas with microsatellite instability often show an absence of hMLH1 protein, [12][13][14] indicating that the tumor with microsatellite instability may be induced by an abnormality of the mismatch repair gene.…”