Clinicopathological evaluation of biological behavior of submucosal invasive gastric carcinomas: relationship among lymph node metastasis, mucin phenotype and proliferative activity.

BACKGROUND Gastric carcinomas have been classified into the differentiated and undifferentiated type, on the basis of its tendency to gland formation. As a result of recent advances in mucin histochemistry, mucin phenotypes of gastric carcinomas have been investigated. However, no consensus on the evaluation of the grade of malignancy of early gastric carcinomas regarding mucin phenotype expression has developed. To address this issue, we evaluated the lymph node metastasis rate and proliferative activity of a submucosal invasive (sm) gastric carcinoma according to mucin phenotype expression. METHODS In resected surgical specimens from 108 patients with a single sm gastric carcinoma, the association between clinicopathological factors and lymph node metastasis was evaluated. In all cases, immunohistochemical staining with human gastric mucin, Muc-2, and CD10 and mucin histochemical staining by paradoxical concanavalin A staining were performed. The mucin phenotypes were classified into gastric-type (G-type), intestinal-type (I-type), mixed gastric and intestinal type (M-type), or a lack of mucin (LOM), using these as markers. To evaluate the cell proliferative activity of the gastric carcinoma, proliferating cell nuclear antigen (PCNA) staining was also performed. RESULTS The rate of lymph node metastasis was higher for G-type sm carcinomas. A multivariate analysis showed that the G-type and lymphatic invasion were independent factors of lymph node metastasis. However, the PCNA-labeling index (PCNA-LI) was low for G-type carcinomas irrespective of the presence or absence of lymph node metastasis. In I-type carcinomas, PCNA-LI was significantly higher in cases that were positive for lymph node metastasis than in negative cases. CONCLUSION G-type and lymphatic invasion are independent risk factors for lymph node metastasis of an sm gastric carcinoma, and proliferative activity may be a significant parameter for lymph node metastasis in cases with I-type carcinomas.

[1]  T. Akamatsu,et al.  Histochemical demonstration of mucins in the intramucosal laminated structure of human gastric signet ring cell carcinoma and its relation to submucosal invasion , 1990, The Histochemical Journal.

[2]  T. Hattori,et al.  Histogenesis and characteristics of gastric-type adenocarcinomas in the stomach , 2005, Journal of Cancer Research and Clinical Oncology.

[3]  M. Fukuda,et al.  Cell proliferation and differentiation in intramucosal and advanced signet ring cell carcinomas of the human stomach , 2004, Virchows Archiv A.

[4]  A. Yamanoi,et al.  INDICATIONS OF ENDOSCOPIC MUCOSAL RESECTION(EMR)FOR SUBMUCOSAL INVASIVE GASTRIC CANCER WITH SPECIAL REFERENCE TO HISTOPATHOLOGICFINDINGS , 2003 .

[5]  A. Ochiai,et al.  Histologic heterogeneity and mucin phenotypic expression in early gastric cancer , 2001, Pathology international.

[6]  S. Yoshida,et al.  Endoscopic mucosal resection for treatment of early gastric cancer , 2001, Gut.

[7]  M. Koike,et al.  Distinction of differentiated type early gastric carcinoma with gastric type mucin expression , 2000, Cancer.

[8]  K. Okita,et al.  A blind comparison of the effectiveness of endoscopic ultrasonography and endoscopy in staging early gastric cancer , 1999, Gut.

[9]  M. Ikegami,et al.  Mucin histochemical analysis of minute gastric differentiated adenocarcinoma , 1999, Pathology international.

[10]  J. Jass,et al.  MUC1 and MUC2 mucins in flat and polypoid colorectal adenomas. , 1997, Journal of clinical pathology.

[11]  J. Jass,et al.  Significance of MUC1 and MUC2 mucin expression in colorectal cancer. , 1996, Journal of clinical pathology.

[12]  K. Haruma,et al.  Histologic grade and cellular proliferation at the deepest invasive portion correlate with the high malignancy of submucosal invasive gastric carcinoma. , 1995, Oncology.

[13]  M. Noda.  [Characteristics of early gastric cancer accompanied by lymph node metastasis]. , 1995, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology.

[14]  J. Dekker,et al.  Biosynthesis of human colonic mucin: Muc2 is the prominent secretory mucin. , 1994, Gastroenterology.

[15]  Y. Egashira.  [Mucin histochemical study of differentiated adenocarcinoma of stomach]. , 1994, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology.

[16]  T. Hattori,et al.  Association between expression of sialosyl‐Tn antigen and intestinalization of gastric carcinomas , 1993, International journal of cancer.

[17]  Y. Mizuma,et al.  Endoscopic laser treatment for early gastric cancer. , 1993, Endoscopy.

[18]  M. Tatematsu,et al.  Histogenesis of Human Stomach Cancers Based on Assessment of Differentiation , 1992, Journal of clinical gastroenterology.

[19]  S Moriguchi,et al.  Predictors of lymph node metastasis in early gastric cancer , 1992, The British journal of surgery.

[20]  T. Muto,et al.  Lymph node metastasis from early gastric cancer: endoscopic resection of tumour , 1992, The British journal of surgery.

[21]  Kazutomo Inoue,et al.  Problems in the definition and treatment of early gastric cancer , 1991, The British journal of surgery.

[22]  M. Key,et al.  Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[23]  P. Mouradian,et al.  Oncofetal mucin Ml epitope family: Characterization and expression during colonic carcinogenesis , 1991, International journal of cancer.

[24]  Y. Oguro.  Endoscopic Treatment of Early Gastric Cancer , 1991 .

[25]  D. Lane,et al.  Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: An index of cell proliferation with evidence of deregulated expression in some, neoplasms , 1990, The Journal of pathology.

[26]  M. Tatematsu,et al.  Gastric and Intestinal Phenotypic Expression of Human Stomach Cancers as Revealed by Pepsinogen lmmunohistochemistry and Mucin Histochemistry , 1990, Acta pathologica japonica.

[27]  L. Villani,et al.  The foveolar cell component of gastric cancer. , 1990, Human pathology.

[28]  M. Tatematsu,et al.  Pyloric gland phenotypic expression of gastric cancers developing in the rat fundic glandular stomach. , 1989, Carcinogenesis.

[29]  E. Tan,et al.  Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. , 1987, Archives of pathology & laboratory medicine.

[30]  G. Janossy,et al.  Expression of the common acute lymphoblastic leukaemia antigen (CALLA gp100) in the brush border of normal jejunum and jejunum of patients with coeliac disease. , 1985, Journal of clinical pathology.

[31]  T. Hattori.  Morphological range of hyperplastic polyps and carcinomas arising in hyperplastic polyps of the stomach. , 1985, Journal of clinical pathology.

[32]  P. Verroust,et al.  A monoclonal antibody to brush border and passive Heymann nephritis. , 1984, Clinical and experimental immunology.

[33]  M. Tatematsu,et al.  Mucin histochemistry by paradoxical concanavalin A staining in experimental gastric cancers induced in Wistar rats by N-methyl-N-nitro-N-nitrosoguanidine or 4-nitroquinoline 1-oxide. , 1980, Journal of the National Cancer Institute.

[34]  S. Spicer,et al.  Histochemical differentiation of complex carbohydrates with variants of the concanavalin A-horseradish peroxidase method. , 1978, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[35]  Kyoichi Nakamura,et al.  CARCINOMA OF THE STOMACH IN INCIPIENT PHASE , 1968 .

[36]  P. Laurén,et al.  THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. , 1965, Acta pathologica et microbiologica Scandinavica.

[37]  J. Jass,et al.  Significance of MUC1 and MUC2 mucin expression in colorectal cancer. , 1996, Journal of clinical pathology.