Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes
2
조회
0
다운로드
5
인용
0
참고문헌
초록
Background: Gastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear. Methods: MSI status was assessed in 414 cases of gastric cancer sing polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed. Results: Out of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (≥2/high power field, p<0.001), expanding growth patterns (p=0.038), gastric predominant mucin phenotypes (p=0.028), and MUC6 expression (p=0.016). Tumor necrosis (≥10% of mass, p=0.031), tumorinfiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p= 0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197). Conclusions: Our data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.
Abstract
Background: Gastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear. Methods: MSI status was assessed in 414 cases of gastric cancer sing polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed. Results: Out of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (≥2/high power field, p<0.001), expanding growth patterns (p=0.038), gastric predominant mucin phenotypes (p=0.028), and MUC6 expression (p=0.016). Tumor necrosis (≥10% of mass, p=0.031), tumorinfiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p= 0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197). Conclusions: Our data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.
참고문헌 (30)
- Ferlay J, "Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008", Int J Cancer, 127, pp.2893~2917 (2010)
- Thibodeau SN, "Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes", Cancer Res, 56, pp.4836~4840 (1996)
- Boland CR, "A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer", Cancer Res, 58, pp.5248~5257 (1998)
- Yamamoto H, "Gastric cancers of the microsatellite mutator phenotype display characteristic genetic and clinical features", Gastroenterology, 116, pp.1348~1357 (1999)
- Lee HS, "Distinct clinical features and outcomes of gastric cancers with microsatellite instability", Mod Pathol, 15, pp.632~640 (2002)
- Falchetti M, "Gastric cancer with high-level microsatellite instability: target gene mutations, clinicopathologic features, and long-term survival", Hum Pathol, 39, pp.925~932 (2008)
- Beghelli S, "Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers", Surgery, 139, pp.347~356 (2006)
- Hemminki A, "Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy", Gastroenterology, 119, pp.921~928 (2000)
- Alexander J, "Histopathological identification of colon cancer with microsatellite instability", Am J Pathol, 158, pp.527~535 (2001)
- Halvarsson B, "Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers", Am J Clin Pathol, 129, pp.238~244 (2008)
- Greenson JK, "Pathologic predictors of microsatellite instability in colorectal cancer", Am J Surg Pathol, 33, pp.126~133 (2009)
- Seo HM, "Clinicopathologic characteristics and outcomes of gastric cancers with the MSI-H phenotype", J Surg Oncol, 99, pp.143~147 (2009)
- An C, "Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma", Clin Cancer Res, 11(2 Pt 1), pp.656~663 (2005)
- Wirtz HC, "Prognostic value and clinicopathological profile of microsatellite instability in gastric cancer", Clin Cancer Res, 4, pp.1749~1754 (1998)
- Mizoshita T, "Microsatellite instability is linked to loss of hMLH1 expression in advanced gastric cancers: lack of a relationship with the histological type and phenotype", Gastric Cancer, 8, pp.164~172 (2005)
- 김우호, "위암 병리보고서 기재사항 표준화", Journal of Pathology and Translational Medicine, 39(2), pp.106~113 (2005), 대한병리학회
- Japanese Gastric Cancer Association, "Japanese classification of gastric carcinoma: 3rd English edition", Gastric Cancer, 14, pp.101~112 (2011)
- Edge SB, "AJCC cancer staging manual" (2009), Springer
- Tsukashita S, "MUC gene expression and histogenesis of adenocarcinoma of the stomach", Int J Cancer, 94, pp.166~170 (2001)
- Wu MS, "Distinct clinicopathologic and genetic profiles in sporadic gastric cancer with different mutator phenotypes", Genes Chromosomes Cancer, 27, pp.403~411 (2000)
- Jass JR, "Diagnosis of hereditary non-polyposis colorectal cancer", Histopathology, 32, pp.491~497 (1998)
- Lynch HT, "Overview of natural history, pathology, molecular genetics and management of HNPCC (Lynch syndrome)", Int J Cancer, 69, pp.38~43 (1996)
- Pino MS, "Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability", Gastroenterology, 138, pp.1406~1417 (2010)
- Oki E, "Chemosensitivity and survival in gastric cancer patients with microsatellite instability", Ann Surg Oncol, 16, pp.2510~2515 (2009)
- An JY, "Microsatellite instability in sporadic gastric cancer: its prognostic role and guidance for 5-FU based chemotherapy after R0 resection", Int J Cancer, 131, pp.505~511 (2012)
- Lauren P, "The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma: an attempt at a histo-clinical classification", Acta Pathol Microbiol Scand, 64, pp.31~49 (1965)
- Nakamura K, "Carcinoma of the stomach in incipient phase: its histogenesis and histological appearances", Gann, 59, pp.251~258 (1968)
- Ming SC, "Cellular and molecular pathology of gastric carcinoma and precursor lesions: a critical review", Gastric Cancer, 1, pp.31~50 (1998)
- Yamazaki K, "Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations", World J Gastroenterol, 12, pp.3803~3809 (2006)
- 신나리, "Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression", Journal of Pathology and Translational Medicine, 45(1), pp.69~78 (2011), 대한병리학회