title: Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation.
abstract: Undifferentiated or medullary carcinoma is characterized by its distinct histologic appearance and relatively better prognosis compared to poorly differentiated colonic carcinoma. These 2 entities may be difficult to differentiate by light microscopy alone. Only limited immunohistochemical studies investigating medullary carcinoma have been reported. These studies suggest a loss of intestinal differentiation, exemplified by a high percentage of CDX2 negativity. Our aim was to further characterize the immunohistochemical profile of medullary carcinoma, with particular emphasis on intestinal markers. Paraffin blocks from 16 cases of medullary carcinoma and 33 cases of poorly differentiated colonic carcinoma were retrieved, and tissue microarrays were constructed and stained with an immunohistochemical panel including CDX2, CK7, CK20, p53, intestinal trefoil factor 3, chromogranin, synaptophysin, MLH-1, MUC-1, MUC-2, and calretinin. A significantly higher proportion of medullary carcinomas, as opposed to poorly differentiated colonic carcinomas, showed loss of staining for MLH-1 and for the intestinal transcription factor CDX2, in accordance with previous studies. MLH-1 staining was present in only 21% of medullary carcinoma cases compared with 60% of the poorly differentiated colonic carcinoma cases (P = .02), whereas CDX2 was positive in 19% of medullary carcinomas and 55% of poorly differentiated colonic carcinomas (P = .03). Interestingly, calretinin staining was strongly positive in 73% of medullary carcinomas compared to only 12% of poorly differentiated colonic carcinomas (P < .0001). Evidence of intestinal differentiation by MUC-1, MUC-2, and TFF-3 staining was seen in 67%, 60%, and 53% of the medullary carcinomas, respectively. These 3 markers were frequently positive in many of the CDX2-negative medullary carcinoma cases. Medullary carcinoma of the colon retains a significant degree of intestinal differentiation as evidenced by its high percentage of staining for MUC-1, MUC-2, and TFF-3. Calretinin, MLH-1, and CDX2 may help to differentiate medullary carcinoma from poorly differentiated colonic carcinoma of the colon.
authors.affiliation: Department of Pathology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Brody
authors.initials: B
authors.lastname: Winn
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Tavares
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fanion
authors.forename: Lelia
authors.initials: L
authors.lastname: Noble
authors.forename: John
authors.initials: J
authors.lastname: Gao
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D064032:Calbindin 2; D018276:Carcinoma, Medullary / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D054338:Cell Transdifferentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C576764:CALB2 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D064032:Calbindin 2; D018398:Homeodomain Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D064030:S100 Calcium Binding Protein G; D000070957:MutL Protein Homolog 1