Expression of Matrix Metalloproteinase-1,2,3 and Type IV Collagen in Gastric Adenocarcinoma : Influence on Lymph Node Metastasis and Prognosis

Jung, Eun-Sune,Kim, Byung-Kee 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

Background : During tumor invasion and metastasis, cancer cells traverse the barriers of the extracellular matrix, basement membranes and interstitial stroma, and gain access to the lymphatics and blood vessels for further dissemination. Although matrix metalloproteinase (MMP) is believed to play an important role in these processes of several solid tumors, little is known in the gastric adenocarcinoma. Methods : Immunohistochemical staining using monoclonal antibodies to MMP-1(interstitial collagenase), MMP-2(type IV collagenase), MMP-3(stromelysin) and type IV collagen were performed in eighty paraffin blocks of the primary gastric adenocarcinoma tissue, and analysed the correlation with lympn node metastasis and survival. Gastric adenoma and benign gastric ulcer tissues were used as control. Results : 1. The immunoreactivity for MMP-1 in the gastric adenocarcinoma was observed in the stromal fibroblasts, cancer cells, neutrophils and monocytes. The increased immunoreactivity was not correlated with lymph node metastasis(P=0.4170), but correlated with prognosis(P=0.0063). 2. The immunoreactivity for MMP-2 in the gastric adenocarcinoma was observed in the stromal fibroblasts and vascular basement membranes. The increased immunoreactivity was correlated with lymph node metastasis(P=0.0517, Odd's ratio=2.274) and prognosis(P=0.0001). 3. The immunoreactivity for MMP-3 in the gastric adenocarcinoma was observed in the stromal fibroblasts and ascular basement membranes. The increased immunoreactivity was not correlated with lymph node metastasis(P=0.4508), but correlated with prognosis(P=0.0003). 4. The immunoreactivity for type IV collagen in the gastic adenocarcinoma was observed in the vascular basement membranes and tumor basement membranes. The decreased immunoreactivity was correlated with lymph node metastasis(P=0.0002, Odd's ratio=0.194) and prognosis(P=0.0001). 5. The intensity of immunohistochemical staining for MMP-2 in the gastric adenocarcinoma is inversely correlated with that of type IV collagen(Kendall's Tau-b correlation =0.37482, P=0.0001). Conclusion : Our results suggest that MMP-1, 2, 3 are important prognostic factors in human gastric adenocarcinoma. The increased immunoreactivity of MMP-2 and the decreased immunoreactivity of type IV collagen show statistically significant correlation with lymph node metastasis and prognosis. This suggest that the inverse correlation with MMP-2 and type IV collagen is important role in lymph node metastasis of gastric adenocarcinoma. The mechanism responsible for the production of MMP by the host fibroblasts remain obscure and require further investigation. (Korean Journal of Pathology 33(4):251-258, 1999)

위 이형성증과 선암종에서 CEA, AgNORs 및 PCNA의 진단적 의의

한원철,문형배 대한병리학회 1995 Journal of Pathology and Translational Medicine Vol.29 No.1

위선종 및 위암 조직에서의 DNA 이중사슬 절단

김정호 ( Jeong Ho Kim ),김성수 ( Sung Soo Kim ),변상원 ( Sang Won Byun ),장영준 ( Young Jun Chang ),김진수 ( Jin Su Kim ),김재광 ( Jae Kwang Kim ),조항주 ( Hang Joo Cho ),임근우 ( Keun Woo Lim ),정은선 ( Eun Sun Jung ) 대한소화기학회 2010 대한소화기학회지 Vol.55 No.1

목적: DNA 이중사슬 절단은 DNA 손상의 한 형태로서 p53 돌연변이 등이 있는 세포에서 치유되지 않은 DSB가 핵 내에 축적될 경우 염색체 불안정을 유도하거나 혹은 암 발생 관련 유전자의 돌연변이 과정을 통해 암세포로 변환될 수 있다. 이에 이번 연구는 암 주위 정상, 선종 및 위암 조직에서 DNA 이중사슬 절단의 표지자인 53BP1과 γ-H2AX단백의 발현 양상을 관찰하였다. 대상 및 방법: 위절제술을 받았던 121예의 위암 환자와 내시경하 점막하 박리술을 받았던 51예의 위선종 환자를 대상으로 각각 tissue microarray를 만든 후 53BP1과 γ-H2AX 단백 각각에 대한 항체로 면역조직화학염색을 하여 발현 지수를 측정하였다. 결과: 53BP1과 γ-H2AX는 암 주위 정상 조직에 비해 위암 조직에서 발현율이 높았으나(p<0.01), 암 주위 정상 조직과 위선종 조직 간에 53BP1과 γ-H2AX 단백의 발현은 차이가 없었다. 위선종 조직에서 53BP1는 이형성 등급 I에 비해 II 및 III의 발현지수가 유의하게 높았다. 위암 환자에서 임상-병리학적 인자는 53BP1 및 γ-H2AX 단백의 발현과 상관관계가 없었다. 결론: 이상의 결과로 보아 DNA 이중사슬절단은 위암 발생과정에 관여하는 것으로 보이나 위선종 세포에서는 별다른 역할을 하지 않는 것으로 보인다. Background/Aims: DNA double strand break (DSB) is one of the critical types of DNA damage. When un-repaired DSB is accumulated in the nucleus of the cells having mutations in such genes as p53, it will lead to chromosomal instability and further more to mutation of tumor-activating genes resulting in tumorogenesis. Some of malignant cancers and its premalignant lesions were proven to have DSB in their nuclei. The aim of this study was to define the differences in expression of 53BP1 and γ-H2AX, the markers of DSB, among normal, gastric adenoma, and gastric adenocarcinoma tissues. Methods: Tissue microarray was made with the tissues taken from 121 patients who underwent gastrectomy for gastric adenocarcinoma, and 51 patients who underwent endoscopic mucosal resection for gastric adenoma. Immunochemical stain was performed for the marker of DSB, 53BP1 and γ-H2AX in the tissue microarray. The normal tissues were collected from histologically confirmed tissues with no cellular atypia obtained from the patients with gastric adenocarcinoma. Results: In gastric carcinoma cells, 53BP1 and γ-H2AX were highly expressed as compared to normal epithelial cells and gastric adenoma (p<0.01). There were no differences in the expression of 53BP1 and γ-H2AX between normal epithelium and gastric adenoma. The expression of 53BP1 in the adenoma with grade II and III atypism was more elevated than in those with grade I atypism. The expression of 53BP1 and γ-H2AX were not significantly different according to the clinicopathologic parameters in the patients with gastric adenocarcinoma. Conclusions: The DSB in DNA seems to be associated with the development of gastric adenocarcinoma, but does not affect the premalignant adenoma cells. (Korean J Gastroenterol 2010;55:19-25)

Expression of β-arrestin 1 in Gastric Cardiac Adenocarcinoma and its Relation with Progression

Wang, Li-Guang,Su, Ben-Hua,Du, Jia-Jun Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Objective: Arrestins act as mediators of G protein-coupled receptor (GPCR) desensitization and trafficking, also actin as a scaffold for many intracellular signaling network. The role that ${\beta}$-arrestin 1 plays in gastric cardiac adenocarcinoma (GCA) and its clinicopathologic significance are untouched. Methods: Fifty patients with gastric cardiac adenocarcinoma were retrospectively enrolled and ${\beta}$-arrestin 1 was detected using immunohistochemistry in tissue samples. Results: Nuclear expression of ${\beta}$-arrestin 1 was observed in 78% of GCA samples (39/50) and cytoplasmic expression in 70% (35/50). ${\beta}$-arrestin 1 could be found in both nucleus and cytoplasm of 54% GCA (27/50) or in either of them in 94% (47/50). ${\beta}$-arrestin 1 protein positivity in well/moderately differentiated carcinomas was significantly higher than that in poorly differentiated carcinomas (P=0.005). We found increased expression of ${\beta}$-arrestin 1 in cytoplasm was correlated with lymph nodal metastasis (P=0.002) and pathological lymph nodal staging (P=0.030). We also found ${\beta}$-arrestin 1 to be over-expressed in glandular epithelia cells of mucinous adenocarcinoma, a tumour type associated with an adverse outcome of gastric cardiac adenocarcinoma (P=0.022). Conclusion: ${\beta}$-arrestin 1 is over-expressed in the nucleus and/or cytoplasm of gastric cardiac adenocarcinoma. However, ${\beta}$-arrestin 1 has no relationship with the prognosis of gastric cardiac adenocarcinoma (P>0.05). Our data imply that ${\beta}$-arrestin 1 in cytoplasm may be involved in differentiation and metastasis of gastric cardiac adenocarcinoma.

진행성 위암에 동반된 위 칸디다증 1예

이두영,김성호,선제형,박진석,손존광,선홍주,이승,박찬국 朝鮮大學校 附設 醫學硏究所 2004 The Medical Journal of Chosun University Vol.29 No.2

Gastric candidiasis is an uncommon disorder. It is an opportunistic pathogen in immune compromised individuals, alcoholics, persons treated with broad-spectrum antibiotics, immunosuppressive and chemotherapeutic agents. Besides, the use of drugs that reduce the gastric acid production may be a cause of gastric candidiasis. We experienced a case of gastric candidiasis following advanced gastric adenocarcinoma. A 85-year-old woman was admitted to our hospital because of epigastric soreness. Endoscopic findings revealed a large ulcero-infiltrating mass with yellow exudate at cardia of the stomach, which suggested an advanced gastric cancer. Endoscopic biopsy revealed spores and pseudohyphae infiltrating through the ulcerated stomach wall, diffuse infiltration of tumor cells and abortive tumor glands. After treatment with fluconazole 100 mg daily for 21 days, no evidence of the gastric candidiasis was seen on endoscopic biopsy and pathologic findings. The case is herein reported of gastric candidiasis following advanced gastric adenocarcinoma along with a review of corresponding literature.

위선암에서 p53 단백의 과발현과 임상 및 병리학적 예후인자와의 상관관계

서병조,유항종,이주호,주미,이혜경,김진복 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.2

Objective: Mutations in the p53 gene, one of the most common genetic alterations in human cancer, are implicated in tumorigenesis and tumor progression. Wild-type p53 negatively regulates the cell cycle; a loss of function by mutation might be expected to result in enhanced proliferating activity and tumor progression. A large number of immunohistochemical studies have confirmed p53 accumulation to be a very common feature of human malignancy. The aim of the present study was to determine whether p53 status in gastric cancer is correlated statistically with various histopathological indicators or not. Methods and Materials: A total of 197 surgically resected gastric adenocarcinomas were examined to determine whether a correlation exited between immunohistochemical expressions of the p53 protein and other histopathological factors. Results: p53 overexpression was observed in 46.2% of the gastric cancers. Overexpression of p53 was correlated with vascular invasion of gastric cancer(p=0.004). In early gastric cancer, the p53 overexpression rate was 42.3%, and of them, a correlation was found between the intestinal type of the Lauren classifcation(p=0.013) and histologically differentiated gastric cancer(p=0.014). Conclusion: p53 overexpression was significantly correlated with vascular invasion of gastric cancer. In cases of early gastric cancer, p53 overexpression was correlated with Lauren classification and differentiation. These results suggest that p53 mutation plays an important role in carcinogenesis in gastric adenocarcinomas. Further study in needed to determine the correlation between p53 overexpression and the prognosis for the gastric cancer patient.

위암의 진행에 따른 Fas관련 아포프토시스 유도의 상관성

임성철,황철기,오서진 조선대학교 부설 의학연구소 2000 The Medical Journal of Chosun University Vol.25 No.1

Background and Objectives : The purpose of this study is to determine whether human gastric adenocarcinomas express Fas-L, sFas-L or Fas , whether serum sFas-L leyel is changed in gastric cancer patients after gastrectomy, whether Fas-L expression is associated with increased apoptotic induction, especially, tumor-infiltrating Iymphocytes(TIL) and whether apoptotic induction is associated with the tumor stage and histologic type. Materials and Methods : The author analysed 38 cases of early gastric carcinoma(EGC) and 61 cases of advanced gastric carcinoma (AGC) which received gastric resection from 1997 to 1998. Of them, the number of diffuse type is 38 cases and the number of intestinal type is 61 cases. The author used immunohistochemical staining for Fas, Fas L and CD45, TACS^TM in situ apoptosis detection kit, and sFas ligand ELISA kit. Results : Fas-L was localized to neoplastic cells in 23 cases (23/38; 61%) of EGC group and 40cases (40/61; 66%) of AGC group. The extent of Fas-L expression was variable, with both Fas-L was localized to neoplastic cells in 23 cases (23/38; 61%) of EGC group and 40 cases(40/61; 66%) of group. The extent of Fas-L expression was variable, with both FasL-positive and negative neoplastic region cccuring within. TIL were detected by co-expression of CD4S and TACS on serial histologic sections. TIL adjacent to Fas-L erxressing tumor regions were decreased in number and TIL adjacent to FasL-negative tumor regions were increased in number; apoptotic induction of TIL showed the opposite pattern (p<05). Fas expression was found essentially homogeneously throughout the tumor mass independent of tumor stage. Fas expression showed 39 cases (39/61; 64%) of intestinal type and 26 cases (26/38; 68%) of diffuse type. Labeling indces for tumoral apoptosis in EGC and AGC were 6.72% and 7.13%, respectively and this difference was statistically insignificant. Co-expression of Fas-L and Fas, which occurred over large areas of the tumors, did not result in an enhanced rate of tumor cell apoptosis. The mean serum sFas-L level was significantly higher in patients before treatment compared with controls, whereas in post-gastrectomy patients, it was significantly lower, In addition, tumor stage and other prognostic factors were not associated with Fas and Fas-L expression, serum sFas-L level, number of TIL and apoptotic induction. Conclusion: 'The author demonstrates a statistically significant reduction of TIL concomitant with significantly increased TIL apoptosis adjacent to FasL-expressing regions of gastric adenocarcinomas. Also an elevated level of ·serum sFas-L in the gastric adenocarcinoma group was noted. These findings suggest Fas-mediated apoptotic depletion of TIL in response to Fas-L expression by stomach cancers, and provide the evidence to support the Fas counter-attack as a mechanism of immune escape in gastric cancer. And These findings indicate that the serum sFas-L level is a useful indicator in evaluating postoperative follow-up. In addition, gastric carcinoma cells of the intestinal and diffuse type did not differ in their expression of the Fas-apoptotic system.

위선종, 위선암종에서 c-erbB-2, c-met 단백 발현

이승우 ( Seung Woo Lee ),강상범 ( Sang Beom Kang ),김연수 ( Yon Soo Kim ),남순우 ( Soon Woo Nam ),이동수 ( Dong Soo Lee ),이혜경 ( Hye Kyung Lee ),한석원 ( Sok Won Han ) 대한소화기학회 2007 대한소화기학회지 Vol.49 No.3

목적: 내시경 또는 외과수술로 절제된 위선종 또는 위선암종 조직을 대상으로 면역조직화학 염색을 이용하여 세포증식에 관여하는 c-erbB2, c-met 단백의 발현 정도를 비교 관찰함으로써 이들 단백이 위선종 및 위선암종의 발생 과정 및 진행에 관련이 있는지를 알아보았다. 대상 및 방법: 위선종 조직 43예와 위선암종 조직 44예를 대상으로 하였다. 모든 조직들은 단클론 항 c-erbB-2, c-met 항체들을 이용하여 면역조직화학염색을 하였다. 결과: c-erbB-2 발현율은 위선종 (91%)에서 위선암종(30%)에 비하여 높았으며 위암에서 미만형(10%)보다 장형(46%)에서 높은 발현율을 보였다. c-met 발현율은 위선종(49%)보다 위선암(77%)에서 높았으며, 위선종에서는 고등급 형성이상군(94%)에서 저등급 형성 이상군(22%)보다 높은 발현율을 보였다. 위암에서는 림프절전이가 있는 경우(89%)가 없는 경우(56%)보다 높았다. 결론: c-erbB-2는 위암의 발생과정 중 초기단계에 관련이 되어있으며 위암에서는 장형위암과 관련이 있다. c-met 단백은 위암에서 림프절 전이와 관련이 있다. 이 두 종양유전자가 위암에서 발현되었을 때 의미하는 바는 서로 다르지만 위암 발생에서 중요한 역할을 한다고 생각한다. Background/Aims: The aim of this study was to investigate the immunohistochemical overexpression of c-erbB-2 and c-met proteins according to the histopathological parameters such as grade of dysplasia, histological type, depth of invasion, lymph node metastasis, and TNM stage in gastric adenoma and gastric adenocarcinoma. Methods: Immunohistochemical staining using monoclonal c-erbB-2 and c-met antibodies was performed on paraffin embedded specimens in 43 adenomas and 44 adenocarcinomas. Results: The expression rate of c-erbB-2 was higher in adenomas (91%) than adenocarcinomas (30%). The expression rate of c-met was higher in adenocarcinomas (77%) than adenomas (49%). In adenoma, the expression rate of c-met was higher in high grade dysplasia (94%) than in low grade dysplasia (22%). In adenocarcinoma, c- met expression was significantly related with lymph node metastasis. Conclusions: c-erbB-2 would be involved in the development of relatively early stage gastric carcinogenesis. c-erbB-2 is related with histologic type and c-met with lymph node metastasis in gastric carcinomas. Although meaning for the experession of these proteins in gastric carcinomas would be different, these proteins may play as important oncogenes in gastric carcinogenesis. (Korean J Gastroenterol 2007;49:152-157)

위선종 및 위선암 조직에서 Rb, p16, Cyclin D1 단백질의 발현

김창섭,최종영,김상우,양영상,정인식 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.32 No.2

Gastric-Type Extremely Well-Differentiated Adenocarcinoma of the Stomach: A Challenge for Preoperative Diagnosis

주미,한송희 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.1

Gastric-type extremely well-differentiated adenocarcinoma (EWDA) is a rare type of gastric adenocarcinoma characterized by infiltration of well-formed mucinous glands with little or no nuclear atypia, which resemble foveolar epithelium or pyloric glands. Because of its high degree of differentiation, preoperative biopsy diagnosis of gastric-type EWDA is very difficult. We encountered a case of gastric-type EWDA, manifesting as a Borrmann type 4 lesion, in a 47-year-old man. Despite four repeated biopsies, the preoperative biopsy diagnosis was not conclusive due to the scarcity of diagnostic tumor cells and lack of knowledge regarding the unusual histologic findings of gastric-type EWDA. We herein describe the histologic findings of gastric-type EWDA in detail, with the aim of facilitating a preoperative biopsy diagnosis and understanding of this rare type of gastric adenocarcinoma.