An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: II. Expression of MUC1, MUC2, MUC5AC, and MUC6 in normal mucosa and in 42 cases

Abstract

Expression of MUC apomucins has rarely been investigated in the signet-ring cell carcinoma (SRCC) of the stomach and colorectum. The author examined immunohistochemically the expression status of MUC1, MUC2, MUC5AC, and MUC6 in 30 cases of gastric SRCC and 12 cases of colorectal SRCC. The normal distribution of these MUC apomucins was also examined in the non-tumorous parts of the stomach and colorectum. In normal tissues, the stomach epithelial cells consistently expressed MUC2, MUC5AC, MUC6, but consistently not MUC1. In colorectum, cryptal epithelial cells consistently expressed MUC2, but consistently not MUC1, MUC5AC, and MUC6. The expression pattern of the gastric SRCC was as follows: MUC1, 3/30 (10%); MUC2, 4/30 (13%); MUC5AC, 20/30 (67%), and MUC6 21/30 (70%). The expression pattern of the colorectal SRCC was as follows: MUC1, 5/12 (42%); MUC2, 11/12 (92%); MUC5AC, 4/12 (33%); and MUC6, 0/12 (0%). Significant differences (p<0.05) were found in the expression of MUC1 (stomach SRCC 10% vs colorectal SRCC 42%), MUC2 (13% vs 92%), MUC5AC (67% vs 33%), and MUC6 (70% vs 0%). Thus, there was a significant tendency that primary gastric SRCC express MUC5AC and MUC6 but not MUC1 and MUC2, while primary colorectal SRCC express MUC1, MUC2 and MUC5A, but not MUC6. These different expressions of these MUC apomucins in gastric and colorectal SRCC seem useful to determine the primary site of metastatic SRCC and for differential diagnosis of SRCC of other sites. In the gastric SRCC, the up-regulation of MUC1 and the down-regulation of MUC2, MUC5AC and MUC6 appear to be associated with carcinogenesis, malignant potential, progression, and clinical behaviors in gastric SRCC. In the colorectal SRCC, the up-regulation of MUC1 and MUC5AC may be associated with carcinogenesis, malignant potential, progression, and clinical behaviors in colorectal SRCC. A comparative review of the present SRCC and presently reported ordinary adenocarcinoma and SRCC cases of the stomach and colorectum was performed.

Keywords: MUC; Signet-ring cell carcinoma; colorectum; histopathology; immunohistochemistry; mucins; stomach.

Figure 1

Histology and histochemistry of primary signet-ring cell carcinoma of the stomach. A. Lower power view. The signet-ring features such as abundant intracytoplasmic mucins, ample and clear cytoplasm, and eccentrically located nuclei compressed by intracytoplasmic mucins are apparent. The signet-ring cell carcinoma is medullary and the stroma is scant in amount. HE: x100. B. High power view. The signet-ring features such as abundant intracytoplasmic mucins, ample and clear cytoplasm, and eccentrically located nuclei compressed by intracytoplasmic mucins are apparent. HE: x400. C. Combined d-PAS and AB stains revealed abundant intracytoplasmic mucins composed of neutral (Mazenta color) and acidic (blue color) mucins. Combined d-PAS/AB double staining: x200.

Figure 2

Immunohistochemical findings of the normal stomach. No expression of MUC1 was seen in any cell types of the normal stomach. Expression of MUC2 (A), MUC5AC (B), and MUC6 (C and D) were consistently recognized in the normal stomach. The expression of MUC2 was mainly seen in the goblet cells of the intestinal metaplasia of the stomach, but it is also noted in non-goblet cells of foveolar epithelium in the stomach (A). MUC5AC expression is seen only in the foveolar cells of the normal stomach (B). MUC6 expression is seen in the foveolar epithelial cells (C) and in the pyloric glands (D) in the normal stomach. Immunostaining, x300.

Figure 3

Immunohistochemical findings of the normal colon. In the colorectum, no expression of MUC1, MUC5AC, and MUC6 was seen in any cell types of the colorectum. In contrast, MUC2 expression is consistently recognized in the cryptal epithelial cells. Immunostaining, x300.

Figure 4

Immunohistochemical findings of primary gastric signet ring cell carcinoma. There are positive expressions of MUC1 (A), MUC2 in (B), MUC5AC (C), and MUC6 (D). Immunostaining, x400.

Figure 5

Immunohistochemical findings of primary colorectal signet ring cell carcinoma. There are positive expressions of MUC1 (A), MUC2 (B), and MUC5AC (C). No MUC6 expression is present. Immunostaining, x400.