The relationship among PDX1, CDX2, and mucin profiles in gastric carcinomas; correlations with clinicopathologic parameters

Abstract

Purpose: Several studies performed on pancreatic-duodenal homeobox 1 (PDX1) have demonstrated a loss of expression and negative tumor modulator effect in gastric carcinoma. Relations between PDX1 and gastric metaplasia, differentiated type of gastric carcinoma, and the early stage of the disease have been exhibited in previous reports. The aim of this study was to examine expressions of PDX1, caudal type homeobox 2 (CDX2) and mucin (MUC) profiles to address the role of PDX1 in gastric carcinogenesis and its relationship with CDX2.

Methods: Seventy gastrectomy specimens were analyzed immunohistochemically for PDX1, CDX2, MUC2, MUC5AC, and MUC6 expressions. The sum of cytoplasmic and nuclear PDX1 immunostaining and PDX1 positivity were assessed. All of the antibodies were examined for a correlation with tumor type, clinicopathologic parameters, and metaplasias. The relation of Ki-67 proliferation index with the expression profiles was also investigated.

Results: Neither PDX1 (66/70) nor CDX2 (37/70) and the mucin profiles (MUC2:11/70, MUC5AC:48/70, MUC6:41/70) showed a significant difference between differentiated and undifferentiated types of gastric carcinoma and clinicopathologic parameters. The PDX1 expression frequency was 94.3%, with an average PDX1 score of 8.8 ± 4.2. PDX1 and CDX2 expression showed a significant difference (P = 0.026 and P = 0.002, respectively) among the phenotypic classification of gastric carcinomas. All of the gastric and intestinal mixed-phenotype gastric carcinomas (GI-type) showed both PDX1 and CDX2 immunopositivity. Except for the relation of PDX1 score with MUC6 expression, no significant difference was detected between PDX1 and CDX2, MUC2, and MUC5AC expressions. A relationship between CDX2 and MUC2 and also between MUC5AC and MUC6 was found statistically. The Ki-67 proliferation index revealed a significant positive correlation with PDX1, CDX2, and MUC2 positivity.

Conclusions: PDX1 expression revealed a higher positivity in gastric carcinomas than the previous studies and showed no relation with tumor type, clinicopathologic parameters, CDX2 expression, or mucin profiles. However, a significant relation of PDX1 and CDX2 expressions among phenotypic classification of gastric carcinomas reveals an idea about similar functions for PDX1 and CDX2 in the evolution of gastric carcinoma.

Fig. 1

Histological classification of gastric carcinomas: a differentiated type adenocarcinoma with papillary and complex tubular pattern (H&E, original magnification ×10), b undifferentiated type adenocarcinoma with well and poorly defined malignant mucinous glands (H&E, original magnification ×20), c differentiated type gastric carcinoma with well to moderately differentiated glands (H&E, original magnification ×20), d signet ring cell carcinoma (undifferentiated type) with a desmoplastic stromal reaction (H&E, original magnification ×10)

Fig. 2

Correlation of overall PDX1 score with age

Fig. 3

PDX1 immunostaining patterns: a moderate intensity of nuclear (arrows) and cytoplasmic immunopositivity in a differentiated type (papillary) adenocarcinoma (IHC, original magnification ×10), b low power view of PDX1 staining with strong cytoplasmic immunopositivity in a differentiated type adenocarcinoma (IHC original magnification ×5), c strong positivity on the mucinous carcinoma cells with PDX1 (IHC, original magnification ×5), d strong nuclear and cytoplasmic immunohistochemical expression (IHC, original magnification ×20)

Fig. 4

PDX1 immunostaining patterns: a strong nuclear (arrows) and weak cytoplasmic immune expression on differentiated type adenocarcinoma (IHC, original magnification ×10), b, c undifferentiated type adenocarcinoma with strong nuclear PDX1, moderate cytoplasmic positivity (arrows) (IHC, original magnification ×20), d weak nuclear and strong cytoplasmic immunopositivity on the signet ring cells (IHC, original magnification ×40)

Fig. 5

CDX2 (a, b) MUC2 (c, d) immunostaining patterns: a strong nuclear CDX2 immunopositivity in a differentiated type gastric carcinoma (IHC, original magnification ×10), b nuclear expression of CDX2 in an undifferentiated type gastric carcinoma (IHC, original magnification ×10), c strong cytoplasmic MUC2 immunopositivity in a mucinous adenocarcinoma (IHC, original magnification ×10), d signet ring cells with strong, scattered MUC2 positivity (IHC, original magnification ×20)

Fig. 6

MUC5AC (a, b), MUC6 (c, d) immunostaining patterns: a high power view of cytoplasmic MUC5AC expression in carcinoma cells (IHC, original magnification ×20), b focal MUC5AC expression on a tumoral gland of the differentiated type gastric carcinoma (IHC, original magnification ×10), c differentiated type gastric carcinoma with focal cytoplasmic MUC6 positivity (IHC, original magnification ×10), d positivity for MUC6 in signet ring cells (IHC, original magnification ×20)