P53 protein immunohistochemical expression in colonic adenomas with and without associated carcinoma

Objectives: P53 protein immunohistochemical (IHC) expression was investigated in a series of colonic adenomas and carcinomas to determine the p53 immunohistochemical expression of adenomas in general compared with carcinomas, the difference in staining pattern between adenomas with associated carcinoma and those without associated carcinoma, and the difference in p53 staining in the usual adenomas (low-grade dysplasia) compared with those harboring high-grade dysplasia.
Methods: The study involved a series of 20 adenomas without concurrent carcinoma (group 1 adenoma), 29 adenomas with concurrent carcinoma (group 2 adenoma), and 20 carcinomas. Sections of the paraffin-embedded tissues were stained with DO-7 p53 monoclonal antibody after microwave antigen-retrieval method. Cases with nuclear staining in ≥ 20% of the tumor cells were considered positive.
Results: Analysis of results showed that 65% of carcinomas and 37% of all adenomas were reactive with p53 IHC staining (   p = 0.03  ). With respect to the adenomas, 30% of group 1 and 41% of group 2 adenomas were reactive for p53 protein (   p = 0.42  ).
Conclusions: Our data demonstrate a statistically significant higher p53 expression rate in colonic carcinomas than in adenomas, and that adenomas with concurrent carcinomas are more frequently p53 positive than those without concurrent carcinoma, but this was not statistically significant. Also, p53 expression is more frequent and intense in adenomas with high-grade dysplasia (10/20, 50%) than in ordinary adenomas with low-grade dysplasia (8/29, 28%), which suggests a strong correlation between the degree of dysplasia in colonic neoplasia and p53 expression pattern.     

大肠肿瘤的基因表达及与细胞凋亡的抑制关系

目的探讨 bcl-2和 P53蛋白在大肠肿瘤中的表达及与细胞凋亡关系。方法用免疫组化方法观察了45例大肠腺瘤和61例大肠癌中 bcl-2和 P53蛋白的表达。结果正常大肠粘膜中 bcl-2和 p53均未见表达,而大肠腺瘤及大肠癌阳性率均较正常明显增加(P<0.01)。大肠腺瘤 p53表达随腺瘤大小增加而增加,其中≥20 mm 组阳性率(77.8%)显著高于<10 mm 组(35.0%,P<0.05)。P53蛋白阳性率也随不典型增生程度增加而增高。p53表达与大肠癌分化程度及 Duke 分期有关。大肠癌细胞凋亡指数与 bcl-2阳性表达呈负相关。大肠腺瘤中 bcl-2和 P53蛋白的表达也呈负相关。结论 bcl-2蛋白表达对大肠癌前病变.腺瘤的增殖有一定意义,p53在大肠腺瘤癌变和大肠癌进展中起重要作用,它们是参与细胞凋亡的良好指标。     

Clinical relevance of proliferation biomarkers and p53 expression in rectal mucosa and sporadic colonic adenomas: a prospective study

BACKGROUND/AIMS: Prospective study to evaluate 1) the pattern of proliferation biomarkers and p53 expression in rectal mucosa and adenomatous tissue, and 2) the clinical relevance of these biomarkers as predictors for adenoma recurrence. METHODOLOGY: 40 patients with sporadic adenomas underwent colonoscopic polypectomy and rectal biopsies. Assessment of proliferation biomarkers--Ornithine decarboxylase, PCNA and Ki-67--was done in adenomas and rectal mucosa, while p53 was performed in adenomas. After polypectomy, 34 adenoma patients were followed for 36 months to detect metachronous polyps. 20 controls underwent colonoscopy and rectal biopsies, with assessment of proliferation biomarkers. RESULTS: Mean values of ornithine decarboxylase, PCNA and Ki-67 in rectal mucosa from adenoma patients were not significantly different when compared with the control group. The expression of these biomarkers was significantly increased in adenomas versus rectal mucosa. Only 6 (15%) out of 40 adenomas were found to overexpress p53 protein. During follow-up, recurrent polyps were detected in 12 patients (relapsing group). Mean values of ornithine decarboxylase, detected at index colonoscopy, were not significantly higher in relapsing group versus non-relapsing group. Mean values of PCNA and Ki-67 detected in adenomas at index colonoscopy were significantly higher in relapsing group when compared with non-relapsing group. Adenoma recurrence was observed in all patients with p53 overexpression. CONCLUSIONS: Ornithine decarboxylase, PCNA and Ki-67 expression in rectal mucosa did not show clinical relevance. Yet, increased expression of PCNA or Ki-67 in adenomatous tissue may be a predictor of adenoma recurrence. Positive p53 might have the same predictive value.     

Overexpression of p53 protein and histologic grades of dysplasia in colorectal adenomas

PURPOSE: To clarify the relation between tumor-suppressor gene p53 expression and histologic grades of dysplasia in colorectal adenomas, we performed immunohistochemical analysis in a series of 59 colorectal polyps and 40 advanced carcinomas. METHODS: Adenomatous polyps were stained by hematoxylin and eosin and classified into mild, moderate, and severe dysplasia (intramucosal carcinoma), according to the World Health Organization's classification. RESULTS: p53 was positive in 7.1 percent (2/28) of mild, 29.4 percent (5/17) of moderate, and 62.5 percent (5/8) of severe dysplasia. In submucosal and advanced carcinomas, positivity rates were 75 percent (3/4) and 47.5 percent (19/40), respectively. Different staining patterns were found, according to grades of dysplasia. In the adenomas with mild or moderate dysplasia, a few focal crypts showed localized p53-positive staining. Adenomas with severe dysplasia had two different staining types. One was a focal staining type as shown in mild or moderate dysplasia; the other was a diffuse staining type, in which glands with mild or moderate dysplasia, surrounding severe dysplasia area, were also stained. Submucosal and advanced carcinomas showed a strong positive staining in cancer cells only. CONCLUSIONS: Overexpression of p53 protein in adenomas with mild or moderate dysplasia and existence of two types of expression in adenomas with severe dysplasia were observed. These facts suggested the possible existence of different pathways in the adenoma to carcinoma progression.     

大肠小扁平腺瘤的形态及病理组织学特征研究

目的探讨大肠小扁平腺瘤的形态学特征及p53、p21、雌激素受体（estrogen receptor，ER）、孕激素受体（progesterone receptor，PR）表达的生物学意义。方法用Olympus CF240型电子结肠镜及OlympusBX41光学显微镜观察50例大肠小扁平腺瘤形态学特征。用免疫组化二步法检测50例小扁平腺瘤及其腺瘤旁组织、26例大肠癌及其癌旁组织、15例正常人大肠黏膜中p53、p21、ER、PR的表达情况。结果小扁平腺瘤发生于大肠任何部位，其发病率依次以横结肠、乙状结肠、直肠为多见；肠镜下见病灶呈圆形或椭圆形，扁平状，基底宽，体积≤1cm。光镜下小扁平腺瘤呈管状腺瘤样图像，上皮具有不同程度的异型增生。小扁平腺瘤中p53、p21、ER、PR的表达率分别为58％（29／50）、56％（28／50）、12％（6／50）、10％（5／50）。随着小扁平腺瘤异型增生程度的增高，p53、p21、ER、PR的表达率也逐渐升高（P〈0．05）。大肠癌中的表达最高（P〈0．05）。结论大肠小扁平腺瘤有其独特的形态学特征，p53、p21、ER、PR的表达与大肠小扁平腺瘤的发生发展有密切关系。     

Growth patterns in various macroscopic types of noninvasive intramucosal colorectal carcinoma with special reference to apoptosis and cell proliferation

PURPOSE: Apoptotic cell death and cell proliferation play important roles in the histogenesis and development of colorectal carcinoma. The aim of this study was to examine the relationship between apoptosis and cell proliferation in various macroscopic types of intramucosal colorectal carcinoma in relation to the expression of p53 and bcl-2. METHODS: One hundred forty cases with endoscopically or surgically resected intramucosal colorectal carcinoma were studied. There were 57 cases of polypoid-type carcinomas, 55 cases of superficial-type carcinomas, and 28 cases of granular-type, laterally spreading tumors. Polypoid-type carcinomas were pedunculated, subpedunculated, or sessile polyps. Superficial-type carcinomas were flat lesions with a smooth, even surface. Granular-type, laterally spreading tumors were superficially spreading lesions with aggregates of nodules and a granular surface. Apoptotic cells were identified by thein situ DNA nick end labeling method. Ki-67, p53, and bcl-2 expression were examined immunohistochemically. RESULTS: The superficial-type carcinoma apoptotic index (30.9 percent) was significantly lower than that of polypoid-type carcinoma (54.4 percent) and granular-type, laterally spreading tumor (60.7 percent). The superficial-type carcinoma proliferative index (67.3 percent) was significantly higher than that of polypoid-type carcinoma (42.1 percent) and granular-type, laterally spreading tumor (28.6 percent). In superficial-type carcinomas the proliferative index in p53-positive carcinomas was significantly higher, and the apoptotic index was higher in carcinomas with a lower proliferative index. There was no significant difference in apoptotic index, proliferative index, or p53 protein overexpression betweende novo carcinomas and those that had arisen in precursor adenomas. CONCLUSIONS: The pattern of cell death and proliferation may vary with different macroscopic types of intramucosal colorectal carcinoma. Superficial-type colorectal carcinomas especially demonstrate diminished apoptosis and increased cell proliferation. This may be useful in understanding their biologic behavior.Read at the Meeting of the American Gastroenterological Association, New Orleans, Louisiana, May 17 to 20, 1998.     

Cyclooxygenase-2 expression according to size and location of gastric and colorectal tubular adenomas]

BACKGROUND/AIMS: Recent studies have shown that cyclooxygenase-2 (COX-2) may be involved in the process of invasion, growth and apoptosis in colorectal carcinoma and in the growth and tumorigenesis in familial adenomatous polyposis. This study was conducted to determine the significance of the expression of COX-2 in gastric and colorectal adenomas. METHODS: Forty-nine samples of gastric adenoma and fifty-seven samples of colorectal adenoma were obtained by endoscopic mucosal resection or polypectomy from 106 patients from January 2000 to July 2003. COX-2 expression was determined by immunohistochemistry. Correlation between COX-2 expression and several clinical factors were compared in each gastric and colorectal adenomas. RESULTS: The expression of COX-2 in epithelial cells was significantly higher in the group with large adenoma (>1 cm) compared with the group with small adenoma (< or =1 cm) in gastric (76.5% vs. 46.7%, p=0.04) and colorectal adenomas (75% vs. 41.5%, p=0.023). Moreover, increased COX-2 expression was shown in distal compared to proximal colorectal adenoma (64.3% vs. 37.9%, p=0.047). CONCLUSIONS: COX-2 was expressed in a size-dependent manner in gastric and colorectal tubular adenomas. The expression of COX-2 was different according to the location of colorectal adenoma. The association of COX-2 expression with the size of adenoma may suggest that the role of COX-2 is not related to the early development of adenoma, but related to the progression of adenoma.     

Clinicopathological features of superficial depressed-type colorectal neoplastic lesions

OBJECTIVE: We performed this study to analyze the endoscopic findings, dissecting microscopic features, and p53 immunostaining in superficial depressed-type (depressed) colorectal neoplastic lesions. METHODS: Dissecting stereomicroscopy was used to ascertain the size and pit pattern of lesions removed by endoscopic snare polypectomy. Immunohistochemical staining of p53 was performed with an antigen retrieval system using a monoclonal antibody to p53. RESULTS: All depressed neoplastic lesions (submucosal carcinoma, n = 6; high-grade dysplasia, n = 14; and adenoma, n = 30) were small (< 1 cm in diameter) and were detected as a depression with or without a marginal elevation on colonoscopic examination. In the dissecting microscopic study, submucosal carcinomas and lesions of high-grade dysplasia almost exclusively showed irregular small pits, with the exception of four malignant lesions with moderate submucosal invasion in which the pit structure was absent. In contrast, adenomas had either regular small (29/30 lesions) or oval pits (1/30 lesions). Rates of p53 positivity were 100%, 64%, and 7% in depressed submucosal carcinomas, lesions of high-grade dysplasia, and adenomas, respectively, thus the prevalence of p53 positivity was significantly higher in the former two groups than in the adenoma group. CONCLUSIONS: The high frequency of invasive carcinoma and high-grade dysplasia found in depressed colorectal neoplastic tumors, despite their small size, indicates that these lesions may be a subtype of colorectal tumor with more aggressive malignant potential at an earlier stage.     

Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

AIM： To investigate the expression of Cyclooxygenase-2 （COX-2）, proliferating cell nuclear antigen （PCNA）, Ki-67 and p53 in gastrointestinal stromal tumors （GISTs） and its relationship with histopathological parameters.
METHODS： Twenty-five GISTs were examined by light microscopy and immunohistochemistry, c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index （MI）, tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53.
RESULTS： COX-2 protein expression was found in 19 of 25 （76%） of the tumors, and expression was noted in the cytoplasm of the tumor cells, p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size.
CONCLUSION： COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.     

Cell Kinetics,p53 and bcl-2 Expression,and c-Ki-ras Mutations in Flat-Elevated Tubulovillous Adenomas and Adenocarcinomas of the Colorectum: Comparison with Polypoid Lesions

Background: Flat(-elevated) tubulovillous adenomas and adenocarcinomas of the colorectum constitute a specific type of neoplasm with superficial spreading growth. To establish their characteristics, a comparative investigation of a series of tumors was performed. Methods: A total of 56 flat tubulovillous tumors (39 adenomas, 17 invasive carcinomas) and 154 polypoid tubular or villous tumors (77 adenomas, 77 invasive carcinomas) were comparatively assessed for cell kinetics and molecular alterations. Results: Ki-67 labeling and p53 expression for both types of tumors increased along with degree of dysplasia or invasion, whereas bcl-2 expression showed an inverse decrease. However, apoptotic activity was invariably low in the flat tubulovillous tumors, as compared with the polypoid tumors, in which increase was apparent with tumor progression. The flat tubulovillous tumors also showed a higher frequency of c-Ki-ras mutations (92.9%) than the polypoid tubular tumors (40.0%). Conclusions: The flat tubulovillous tumor can be considered a distinct entity, with characteristics different from the polypoid counterpart.     

Expression of brain-type glycogen phosphorylase is a potentially novel early biomarker in the carcinogenesis of human colorectal carcinomas

OBJECTIVE: Our previous studies have demonstrated the significant role of brain-type glycogen phosphorylase (BGP) in the carcinogenesis of gastric carcinoma. The aims of the present study were to investigate the expression of BGP in colorectal carcinoma as well as the timing of this expression in the adenoma-carcinoma sequence (ACS), in comparison with the overexpression of p53 protein. We also sought to identify this marker in the particular colorectal mucosa bearing de novo carcinoma. METHODS: The expression of BGP and p53 protein in colorectal carcinoma using affinity purified specific anti-human BGP antibody (Ab) and anti-p53 Ab was studied using 96 resected specimens. Further investigation to examine the timing of BGP expression in comparison with p53 overexpression was carried out using 13, 18, eight, and 16 specimens of adenoma with mild, moderate, and severe dysplasia, and carcinoma in adenoma, respectively. The BGP immunohistochemistry in whole resected human colorectal mucosa (two with carcinoma and one with ulcer) was carried out using specific anti-BGP and anti-p53 Ab. RESULTS: The BGP visualized by immunohistochemistry was commonly present in colorectal carcinoma (83.3%). The expression of this molecule during ACS showed excellent correlation with the increased dysplasia and was found before p53 overexpression, whereas no BGP expression was seen in the normal human large intestine remote from the cancer foci. Positive staining in overtly normal-looking colonic mucosa was observed mainly around carcinomas without any adenoma component. CONCLUSIONS: The present study is the first to localize the BGP molecule in colorectal carcinoma, adenoma, and normal mucosa. It is suggested that BGP is a novel biomarker for carcinogenesis in both the pathways of ACS and the de novo colorectal carcinoma.     

Cell kinetics, p53 and bcl-2 expression, and c-Ki-ras mutations in flat-elevated tubulovillous adenomas and adenocarcinomas of the colorectum: comparison with polypoid lesions.

BACKGROUND: Flat(-elevated) tubulovillous adenomas and adenocarcinomas of the colorectum constitute a specific type of neoplasm with superficial spreading growth. To establish their characteristics, a comparative investigation of a series of tumors was performed. METHODS: A total of 56 flat tubulovillous tumors (39 adenomas, 17 invasive carcinomas) and 154 polypoid tubular or villous tumors (77 adenomas, 77 invasive carcinomas) were comparatively assessed for cell kinetics and molecular alterations. RESULTS: Ki-67 labeling and p53 expression for both types of tumors increased along with degree of dysplasia or invasion, whereas bcl-2 expression showed an inverse decrease. However, apoptotic activity was invariably low in the flat tubulovillous tumors, as compared with the polypoid tumors, in which increase was apparent with tumor progression. The flat tubulovillous tumors also showed a higher frequency of c-Ki-ras mutations (92.9%) than the polypoid tubular tumors (40.0%). CONCLUSIONS: The flat tubulovillous tumor can be considered a distinct entity, with characteristics different from the polypoid counterpart.     

p53 overexpression in flat serrated adenomas and flat tubular adenomas of the colorectal mucosa

The expression of the p53 protein was investigated in flat serrated neoplasias as well as in other histological phenotypes of flat or exophytic hyperplasias or neoplasias of the colorectal, mucosa. A total of 104 such lesions were analyzed: 24 were flat serrated neoplasias (22 flat serrated adenomas and 2 flat serrated adenocarcinomas), 26 flat tubular adenomas, 17 flat hyperplastic polyps, 29 exophytic tubular and/or villous neoplasias (23 adenomas and 6 exophytic adenocarcinomas) and the remaining 8, exophytic hyperplastic polyps. Deparaffinized, rehydrated sections were treated immunohistochemically to detect those overexpressing the p53 protein. Lesions having slight (+), moderate (++) or intense (+++) staining were considered immunoreactive. The results showed that 50% of the flat serrated adenomas with low-grade dysplasia (LGD) and 66.7% of those with high-grade dysplasia (HGD) had p53 immunoreactivity. None of the flat tubular or of the exophytic adenomas with LGD expressed p53, but immunoreactivity was present in 61.5% of the flat tubular adenomas with HGD and in 52.3% of the exophytic adenomas with HGD. All adenocarcinomas had an intense p53 reaction. Weak p53 expression was demonstrated by 11.7% of the flat hyperplastic polyps but none of the exophytic polyps reacted. The occurrence of p53 expression in flat serrated adenomas with LGD suggested that, despite its low histological profile, one-half of those lesions could be biologically already committed to independent growth. The occurrence of p53 expression in nearly 12% of the flat hyperplastic polyps was totally unexpected and deserves further investigation. Flat serrated adenoma emerges as a novel, independent histological entity among the various phenotypes of flat neoplasias of the colorectal mucosa.     

Is p53 immunohistochemistry useful for optimal decision for treatment of polypoid lesions in ulcerative colitis?]

BACKGROUND: Usefulness of p53 staining for the differentiation between adenoma and DALM has been reported recently, so recognizable lesions stained positively can be diagnosed as DALMs. For the cases with DALMs, total colectomy has been thought to be necessary. METHODS: Immunohistochemical staining for p53 was performed in 4 adenocarcinomas and 4 adenomas in ulcerative colitis. RESULTS: Three carcinomas and 3 adenomas were positive. One carcinoma (protruded mucosal cancer) and 3 adenomas (1 flat elevated lesion and 2 laterally spreading tumors) stained positively for p53 were treated only by polypectomy or local excision. The patients have been under surveillance for periods ranging from 1 to 10 years, during which no metachronous dysplasia has developed. CONCLUSIONS: These findings suggest that some groups of the polypoid lesions can be resected locally even if stained positively by p53 immunohistochemistry.     

Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions

AIM: To examine the relationship between cyclooxygenase-2 (COX-2) overexpression and p53 accumulation in gallbladder carcinoma and its precursor lesions. METHODS: Sixty-eight gallbladder tissue samples comprising 14 cases of normal gallblader epithelium, 27 cases of dysplasia (11 low-grade dyplasia and 16 high-grade dysplasia) and 27 adenocarcinomas were evaluated by immunohistochemistry for COX-2 expression and p53 accumulation. The relationship among COX-2 expression, p53 accumulation and clinicopathological characteristics was analysed. RESULTS: COX-2 was expressed in 14.3% of normal gallbladder epithelium, 70.3% of dysplastic epite hlium, and 59.2% of adenocarcinomas. When divided into low- and high-grade dysplasia, COX-2 was positive in 5 (45.4%) cases of low-grade and 14 (87.5%) of high-grade dysplasia (P = 0.019). Accumulation of p53 was detected in 5 (31.2%) cases of high-grade dysplasia and in 13 (48.1%) of carcinomas. No p53 accumulation was found in normal epithelium or low-grade dysplasia. COX-2 overexpression was observed in 17 of 18 (94.4%) cases with p53-accumulation in comparison with 20 (40.0%) out of 50 cases without p53 accumulation (P < 0.001). CONCLUSION: The significant differences in COX-2 expression among normal epithelium, low-grade dysplasia and high-grade dysplasia suggest that overexpression of COX-2 enzyme is an early event in gallbladder carcinogenensis. Furthermore, since accumulation of p53 correlates with COX-2 expression, COX-2 overexpression observed in gallbladder high-grade dysplasia and carcinoma might be partly due to the dysfunction of p53.     

Expression of maspin in colon cancers: its relationship with p53 expression and microvessel density

We studied the expression of maspin in colonic adenocarcinoma compared with adenoma and metastatic adenocarcinoma as well as the relationship with its possible regulator, p53. The colonic specimens consisted of 24 adenomas, 49 adenocarcinomas, and 17 metastatic adenocarcinomas. Immunohistochemical staining of paraffin sections was done with microwave-based antigen retrieval methods. The Ki-67 index and the microvessel density were counted using an image analysis system. Maspin expression was positive in 75.5% of adenocarcinomas and 91.7% of adenomas. Only 47.1% of the nodal metastasis showed positive maspin expression. In colonic adenocarcinomas, p53 expression was positive in 44.7% of the maspin-positive groups compared with 100% of the maspin-negative groups (P < 0.005). Colonic adenocarcinomas with the positive maspin expression groups showed less intense microvessel density (181.1 ± 54.2) than those of the negative maspin expression groups (256.1 ± 75.4, P < 0.001). In conclusion, we demonstrated maspin expression in colon cancer with a sequential decreased expression rate from adenoma to metastatic carcinomas, which signifies the tumor suppressive function of maspin, and an inverse correlation with p53 and microvesel density, which indicates the regulatory effect of p53 on maspin and anti-angiogenesis effect of maspin.     

Cyclooxygenase-2 expression correlates with nuclear p53 accumulation in gastric carcinoma

BACKGROUND/AIMS: COX-2 (Cyclooxygenase-2) is the inducible isoform of cyclooxygenase in response to cytokines, mitogens, and growth factors and may induce carcinogenesis through the mechanisms of inhibiting apoptosis, increasing cell proliferation, and enhancing angiogenesis. This study aimed to clarify the relationship of COX-2 and p53, a well-known tumor suppressor gene, in gastric carcinoma. METHODOLOGY: Immunohistochemical staining of nuclear p53 protein and cytoplasmic COX-2 protein were utilized on tumor tissue sections from 65 surgical specimens. Their correlation was further analyzed according to pathologic characteristics. RESULTS: There were 47% (16/34) of high COX-2 expression in the high p53 immunoreactivity group but only 19% (6/31) of high COX-2 expression in the low p53 immunoreactivity group. COX-2 overexpression significantly correlated with the accumulation of nuclear p53 protein in general (p = 0.035). Analysis based on different pathologic characteristics revealed that COX-2 correlates with p53 in subsets of advanced, cardiac, and H. pylori (-) gastric carcinomas (p = 0.027, 0.048, 0.036, respectively). But the relationship does not differ between Lauren's intestinal- and diffuse-type gastric carcinomas. CONCLUSIONS: Our work provides evidence linking COX-2 and p53 in gastric carcinogenesis, but the mechanism how they interact to promote tumorigenesis remains to be elucidated.     

Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue lymphoma

AIM: To assess the expression of cyclooxygenase-2 (COX-2),nitric oxide synthase (iNOS), p53 and Ki-67 in gastric mucosaassociated lymphoid tissue (MALT) lymphoma and clarify the relationship between COX-2 expression and iNOS or p53 expression in these patients.METHODS: The expressions of COX-2, iNOS, p53 and Ki-67 were detected in 32 gastric MALT lymphoma specimens and 10 adjacent mucosal specimens by immunohistochemical Envision method.RESULTS: COX-2 and iNOS expressions were significantly higher in gastric MALT lymphoma tissues than those in adjacent normal tissues. The expression of COX-2 was observed in 22 of 32 cases of MALT lymphoma tissues (68.8%). A positive cytoplasmic immunoreactivity for iNOS was detected in 17 of 31 cases (53.1%). COX-2 expression in gastric MALT lymphoma tissues was positively correlated with iNOS expression (r=-0.448, P=0.010) and cell proliferative activity analyzed by Ki-67 labeling index (r=0.410, P=0.020).The expression of COX-2 protein did not correlate with age,sex, stage of disease, lymph node metastasis or differentiation.The accumulation of p53 nuclear phosphoprotein was detected in 19(59.4%) of tumors, p53 protein was expressed in 11 of 23 assessed LG tumors and in 8 of 9 assessed HG tumors.The difference of p53 positivity was found statistically significant between LG and HG cases (P=0.0302). The p53 accumulation correlated with advanced clinical stage (stage Ⅲ+Ⅳ vs stage Ⅰ+Ⅱ, P=0.017). There was a significant positive correlation between COX-2 expression and p53 accumulation status (r=0.403,/=0.022). The mean PI of Ki-67 in each grade group were 36.0&#177;7.73% in HG and 27.4&#177;9.21% in LG. High-proliferation rate correlated with HG tumors (r=0.419, P=0.017). The correlation coefficient showed a significant positive correlation between PI and COX-2 expression in MALT lymphoma patients (r=-0.410,P=0.020).CONCLUSION: COX-2 expresses in the majority of gastric MALT lymphoma tissues and correlates with cellular proliferation and iNOS expression. COX-2 overexpression is closely associated with p53 accumulation status, iNOS and COX-2 may play a synergistic role in the pathogenesis of gastric MALT lymphoma.     

Immunohistochemical evaluation of tissue-specific proteolytic enzymes in adenomas containing foci of early carcinoma: correlations with cathepsin D expression and other malignant features

BACKGROUND: Cathepsin D (CD) is an aspartyl lysosomal protease, and the prognostic value of CD expression has been studied in a variety of tumors, however, its role in early adenocarcinomas remains unclear. AIM OF THE STUDY: We evaluated the expression of CD in a series of colorectal adenomas with severe dysplasia containing foci of early carcinoma and compared the results to several histopathological and immunohistochemical features. METHODS: Adenomas were obtained by endoscopic polypectomy from 33 patients. Twenty-four of the 33 adenomas contained well-differentiated adenocarcinomas and nine adenomas contained moderately differentiated adenocarcinomas. RESULTS: Positive CD expressions were observed in 25% of well-differentiated adenocarcinomas and in 66.7% of moderately differentiated adenocarcinomas (p < 0.05). Of the 12 adenocarcinomas with positive CD expression, four had positive CD expression in their adenomas (p < 0.01), 6 showed positive Ki-67 expression in their adenomas (NS), and 10 had positive p53 expression in their adenomas (p < 0.05). No significant association was seen between the level of CD expression and adenoma size. CONCLUSIONS: The expression of CD in adenocarcinoma correlated significantly with differentiation, and with the levels of CD and p53 expression in the adenomas of the polyp.     

Comparative clinicopathological and immunohistochemical study of ras and p53 in flat and polypoid type colorectal tumours.

Mutations in oncogenes and tumour suppressor genes may have an important oncogenic role. Although flat type tumours have been frequently detected in recent years, ras and p53 expressions have not been studied in these tumours. Using a monoclonal and polyclonal antibody to the ras p21 and p53 product, paraffin wax embedded sections of 98 colorectal tumours (43 cases of the flat type colorectal tumour and 55 cases of polypoid type tumour) were stained using the immunoperoxidase technique. Staining was evaluated by light microscopic examination. Positive staining rate of ras p21 for the flat type was 0%; for the polypoid type, it was 60% in cancer with submucosal invasion, 82% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The positive staining rate of p53 for the flat type was 50% in submucosal cancer, 9% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. For the polypoid type, it was 40% in submucosal cancer, 12% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The intermediate staining rate of p53 in the polypoid type was 20% in submucosal cancer and 41% in adenoma with high grade dysplasia. It was seen that p53 was commonly expressed in both flat and polypoid lesions, p21 was not expressed in flat lesions, whereas it was commonly expressed in polypoid neoplasms. In the flat type cancer, a genetic change different from that of the polypoid type cancer is suggested.