M Verdu1,3, R Roman1, M Calvo4, N Rodon1, B Garcia1, M Gonzalez1 and X Puig1,2,3.
1BIOPAT.Biopatologia Molecular, SL, Grup Assistència, Barcelona, Spain; 2Hospital de Barcelona, SCIAS, Grup Assistència, Barcelona, Spain; 3Histopat Laboratoris, Barcelona, Spain and 4Statistics Department, Universitat Barcelona, Barcelona, Spain.
Background: Micropapillary carcinoma (MC) is accepted as an aggressive variant of colorectal adenocarcinoma, described for the first time in the breast and later in other organs. At present, there are a limited number of colorectal MC series reported, not enough to define the molecular profile of this variant.
Design: Clinicopathological features of a cohort of 379 patients with primary colo-rectal cancer were retrospectively reviewed, looking for the presence, quantification and localization of MC pattern (small papillary cell clusters surrounded by lacunar spaces) respect to tumoral mass. The parameters evaluated in each case included: age, sex, location of primary tumor, tumor size, growing pattern, grade, depth of invasion (pT), lymphovascular and perineural invasion, nodal status (pN) and number of positive lymph node. We also assessed the expression of CK7, CK20, CEA, MUC1, EMA, p53 and Miss Match Repair genes (MMR). Likewise, genetic assessment of microsatellite instability (MIN), chromosome 18q status, p53 and Kras mutation were performed on DNA extracted from formalin-fixed, paraffin-embedded samples.
Result: Sixty cases (15.8%) had MC component, ranging from 5 to 95% of the tumor. MC cases presented significantly higher frequency of infiltrative pattern and more positive lymph nodes compared with conventional carcinoma. IHC for MUC1 and EMA makes evident the characteristic inside-out staining pattern of the MC component. Also, these component showed more frequently CK7 expression (16.6 to 3.8%), (p=0.899). In reference to the molecular results, we found statistically significant differences between the two groups on the frequency of p53 alterations (accumulation and/or mutation) (p=0.0343), MIN (p=0.0123), and incidence of RER fenotype (MMR loss and/or MIN) (p=0.0105).
Conclusion: With regard to the histological parameters, colorectal carcinoma, having at least a 5% of MC component, appears to be more aggressive than conventional colorectal adenocarcinoma. A remarkable CK7 expression has been observed in the MC component. Also MC are characterized for presenting p53 alterations, lower incidence of microsatellite instability and RER fenotype. These results support the hypothesis of MC carcinogenesis developing through the classical chromosomic instability pathway.