Villin is a biomarker for reverse polarity in colorectal micropapillary carcinoma

Abstract

Colorectal cancer (CRC) is a common malignant tumor of digestive system. CRC with micropapillary pattern (MPP) is an aggressive variant of colorectal adenocarcinoma. The aim of the present study was to clarify the clinicopathological significance and the prognostic role of an immunohistochemical marker, MPP, in CRC. The association between MPP and clinicopathological characteristics and prognosis in 286 cases of CRC (286/453 cases had follow-up information) were analysed. Then, 81 tissues without MPP and 90 tissues with MPP were analysed by immunohistochemistry using antibodies against villin, E-cadherin and epithelial membrane antigen (EMA). Bioinformatics was used to evaluate the expression of these three indicators in CRC. The proportion of micropapillary carcinoma in the overall tumour was ≥5%, and was observed in 90/453 cases (19.8%). The present data showed that CRC with MPP displayed higher rates of vascular and lymphatic invasion, a higher metastatic lymph node ratio and a higher pathological tumour and metastasis stage compared with CRC without MPP. The positive expression rates of EMA, E-cadherin and villin were 50.3, 93.4 and 96.5%, respectively. In 90 CRC cases with MPP, EMA inside-out pattern (I/OP) staining was observed in 26 cases (28.9%), and it was often focal and partial, while 37 cases (41.1%) had E-cadherin focal and partial staining compatible with reverse polarity. Villin I/OP staining was observed in 77 cases (85.6%), and circumferential staining predominated over partial staining. Overall, the data suggested that the presence of MPP is significantly associated with aggressive tumour behaviour and worse overall survival rate in CRC. Visualization and distinction of reverse polarity of colorectal micropapillary carcinomas is improved villin compared with EMA or E-cadherin.

Association between Immunohistochemistry Markers and Tumor Features and Their Diagnostic and Prognostic Values in Intrahepatic Cholangiocarcinoma

“…However, the prognostic values of these frequently used IHC markers have been largely unknown. Besides, we have previously noticed Villin (an actin modulator in the regulation of cell structure/plasticity and a polarity associated marker which may participate in colorectal micropapillary carcinoma, breast cancer, cholestasis, and pathology in hepatocyte [ 9 – 11 ]) was highly expressed in most of ICC cases. It is reasonable to hypothesize that some important ICC-related proteins have links to the later survival.…”

Molecular Pathology of Micropapillary Carcinomas: Is Characteristic Morphology Related to Molecular Mechanisms?

“…At the same time, MUC1 neutralizes the effects of intercellular adhesion molecules (such as E-cadherin and β-catenin) 31. E-cadherin is a calcium-dependent cell-cell adhesion glycoprotein responsible for epithelial cell integrity 24. A decrease in its expression is associated with the potential for metastasis of tumor cells 18.…”

“…31 E-cadherin is a calcium-dependent cell-cell adhesion glycoprotein responsible for epithelial cell integrity. 24 A decrease in its expression is associated with the potential for metastasis of tumor cells. 18 Loss of E-cadherin expression also supports the hypothesis that reversed cell polarity reflects EMT.…”

“…35 It has been reported that while villin is expressed on the outer surface of tumor clusters with immunohistochemistry, the weak staining pattern in the center helps detect the reverse polarity of IMPC. Villin is a useful marker in diagnosing colon IMPC, and it has high sensitivity in detecting reverse polarity compared with EMA and E-cadherin 24 (Fig. 2D).…”