Comparison of the proliferative capacity of adenomatous hyperplasia and well differentiated hepatocellular carcinoma

The identification of nodular lesions, which used to be difficult to differentiate from well differentiated hepatocellular carcinomas, has become frequent since the advent of ultrasonic-guided liver tumor biopsy techniques. This is because adenomatous hyperplasias, which are regarded as putative precancerous lesions, which needed to be differentiated from malignant lesions, often an a nodular. The histological specimens of 52 tumors, obtained from patients with chronic liver injury, were subjected to immunohistological staining for proliferative cell nuclear antigen (PCNA). Findings obtained by this immunohistological technique were compared with those obtained by histological image analysis. Adenomatous hyperplasias with fatty changes or with a high nuclear cytoplasmic ratio on image analysis were frequently PCNA-positive (P<0.01). These nodular lesions, whose morphological characteristics were similar to those of well differetiated hepatocellular carcinomas, showed a high potential for growth. It seems that PCNA may be a useful indicator for increasing our understanding of the progress from adenomatous hyperplasia to hepatocellular carcinoma.     

Immunohistochemical Study of Colorectal Polyps with Antibodies against CEA,CA19-9, CA125, CA15-3 (DF3), PCNA and p53

Abstract: We analyzed the expression of CEA, CA19-9, CA125, CA15-3 (DF3), PCNA and p53 immunohistochemically in 14 tissue specimens of mucosal cancers in adenoma, seven tubulovillous adenoma specimens, and 16 tubular adenoma specimens. The rates of positive staining for mucosal cancer in adenoma, tubulovillous adenoma and tubular adenoma specimens, respectively, were: for CEA: 100%, 85.7% and 75%; for CA19-9: 71.4%, 71.4% and 56.2%; for CA125:0%, 0% and 0%;for CA15-3 (DF3): 64.3 %, 0% and 0 %; for PCNA: 100%, 88.9% and 56.2%; and for p53: 35.7%, 0% and 0% . The results suggest that the expressions of CEA, CA19-9, CA15-3 (DF3), PCNA and p53 are related to colorectal tumorigenesis. None of the specimens studied showed staining for CA125, suggesting that CA125 is not involved in the early stages of colorectal carcinogenesis. There was no significant difference in the rates of positive staining for CEA and CA19-9 among mucosal cancer in adenoma, tubular adenoma and tubulovillous adenoma specimens. However, the rates of positive staining for PCNA and p53 were significantly higher in mucosal cancer in adenoma specimens than for tubular adenoma specimens (p<0.05), and the rate of CA15-3 (DF3) positive staining was significantly higher for mucosal cancer in adenoma than for tubulovillous adenoma (p<0.01) and tubular adenoma (p< 0.001) specimens. Therefore, the CA15-3 (DF3) antigen is an immunohistochemical marker for colorectal carcinomas. The present results suggest that CA15-3 (DF3), PCNA and p53 play important roles in the genesis of colorectal adenomas.     

Magnifying chromoendoscopy combined with immunohistochemical staining for early diagnosis of gastric cancer

AIM:To assess the diagnostic value of using magnifying chromoendoscopy combined with immunohisto-chemical staining of proliferating cell nuclear antigen (PCNA)and p53 in the detection of gastric precancerous lesions. METHODS:Ninety-five patients who were treated for abdominal discomfort,abdominal pain,bloating,and acid reflux at our hospital from January 2010 to December 2011 were included in the study.An ordinary gastroscopic procedure was initially performed to select the lesions.All subjects underwent magnifying chromo-endoscopy to observe morphological changes of gastric pits.Biopsies were then taken from each area of interest and sent for pathological examination and detection of PCNA and p53 expression by immunohistochemistry. An immunoreactivity score for each lesion was calcu-lated.Based on immunoreactivity scores,immunohisto-chemical staining was then considered. RESULTS:Compared to intestinal metaplasia,gastric pits were more diverse in size,more irregular in shape, and more disorderly in arrangement in moderate and severe dysplasia.PCNA and p53 expression was sig-nificantly higher in precancerous lesions(intestinal metaplasia and dysplasia)than in chronic gastritis. PCNA expression showed an upward trend in types A-F pits.The number of cases that showed strong PCNA positivity increased significantly with an increase in the severity of lesions.Rank sum test for independent samples showed that p53 expression was significantly higher in types E and F pits than in types A-D pits(H =33.068,P=0.000).Rank sum test for independent samples showed that PCNA expression was significantly higher in types E and F pits than in types A-D pits(H =31.791,P=0.001). CONCLUSION:The presence of types E and F pits,in which p53 and PCNA are highly expressed,is highly sug- gestive of the occurrence of early cancer,and patients developing these changes should be closely followed.     

Apoptosis and its relationship with cell proliferation, p53, Waf1p21, bcl-2 and c-myc in esophageal carcinogenesis studied with a high-risk population in northern China

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Increased rectal cell proliferation following alcohol abuse

BACKGROUND: Epidemiological data indicate an increased risk for rectal cancer following chronic alcohol consumption. As chronic ethanol ingestion leads to rectal hyperregeneration in experimental animals, indicating a state of increased susceptibility to carcinogens, we studied cell proliferation in alcohol abusers. METHODS: Rectal biopsies were taken from 44 heavy drinkers and 26 controls. Cell proliferation, including proliferative compartment size, was measured by immunohistological staining for proliferative cell nuclear antigen (PCNA) and Ki67, and by in situ hybridisation for histone H3. Quantification of cell proliferation using PCNA staining was evaluated in 27 alcohol abusers and 12 controls. In addition, immunohistology was performed for cytokeratins and gene products of Rb1, bcl-2, and p53. RESULTS: Heavy drinking resulted in increased cell proliferation of the rectal mucosa, as shown by increased detection of different proliferation markers. However, cell differentiation regarding cytokeratin expression patterns was unchanged as well as regulatory factors involved in carcinogenesis and/or apoptosis. CONCLUSION: Chronic alcohol abuse leads to rectal mucosal hyperproliferation in humans, a condition associated with an increased cancer risk.     

胃癌增殖细胞核抗原、bcl-2基因表达及其与肥大细胞浸润的关系

目的 探讨肥大细胞对胃癌组织生长的影响机制及与增殖细胞核抗原（PCNA）、bcl-2基因的关系。方法 采用阿尔辛蓝-沙红及免疫组织化学染色法,同步检测74例胃癌标本中的肥大细胞数及PCNA、bcl-2基因蛋白的表达。运用图像分析仪对浸润的肥大细胞及PCNA的表达进行定量计数;采用半定量法检测bcl-2的表达。结果 胃癌组织内的肥大细胞主要分布于癌旁交界区。此区肥大细胞的数量显著多于癌内间质区（t=9．11,P〈0．01）,两者呈正相关（r=0．303,P〈0．01）。肥大细胞的数量与PCNA及bcl-2的表达呈显著负相关。有肥大细胞浸润组的PCNA表达指数显著低于无肥大细胞浸润组（P〈0．01）。bcl-2高表达组的癌内间质区肥大细胞数目显著少于bcl-2低表达组。结论 癌间质内肥大细胞数目及类型的变化是肥大细胞参与机体抗肿瘤反应的形态学依据。肥大细胞可通过干扰胃癌组织PCNA、bcl-2的表达,抑制肿瘤细胞的增殖。     

沙土鼠感染幽门螺杆菌后胃粘膜病理学改变的研究

目的和方法:应用HP标准菌株ATCC43504,增菌培养后接种于6周龄沙土鼠胃内。分别于2周、12周后杀死实验鼠。鼠胃经过福尔马林固定,石蜡切片,进行HP组化染色、AB/PAS染色及Brdu.PCNA免疫组化染色。结果:接种HP2周后,胃粘膜上皮细胞间有中性粒细胞、淋巴细胞浸润,上皮细胞及腺窝内可见大量HP存在,AB/PAS染色处见肥大细胞增多。Brdu.PCNA呈阳性表达,明显高于对照组。接种HP12周后,胃窦部出现溃疡(2/3),胃粘膜上皮细胞可见核分裂相及淋巴滤泡。结论:①接种HP2周后的沙土鼠胃粘膜呈急性炎症改变,HP定植于胃窦粘膜呈慢性炎症改变。提示沙土鼠是研究HP感染性胃病有价值的动物模型;②HP感染性胃粘膜Brdu.PCNA呈阳性高表达,表明HP感染过程中,伴有细胞部增值性变化。     

Immunohistological detection of PCNA/cyclin in paraffin-embedded liver tissue

The purpose of this report is to describe an immunohistological method for detection of proliferating cell nuclear antigen (PCNA/cyclin) in formaldehyde-fixed and paraffin-embedded liver tissue and to clarify the effects of formaldehyde fixation on antigenicity of PCNA/cyclin. For the immunohistological investigation, 34 cases (11 hepatocellular carcinoma, 8 liver cirrhosis, 15 chronic hepatitis) of human liver biopsy specimens were stained by the avidin-biotin peroxidase complex (ABC) method using a commercially available monoclonal anti-PCNA/cyclin antibody (Mab, 19A2). The PCNA/cyclin-positive nuclei of normal or transformed hepatocytes were detected in 11 cases of hepatocellular carcinoma (100%), 7 cases of liver cirrhosis (87.5%) and 12 cases of chronic hepatitis (80%). Various formaldehyde fixation conditions were examined for the regenerative rat liver by changing formaldehyde concentration, fixation time and time interval from resection to fixation. In conclusion, we have found that PCNA/cyclin-positive cell rate of the liver was stabilized within the first 7 days of the fixation. These results suggested that an immunohistological method with anti-PCNA/cyclin antibody might be useful for the routine cell kinetic analysis of the liver.     

Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation.

Immunohistochemistry of the S phase related proliferating cell nuclear antigen (PCNA) was studied as an alternative to ex-vivo bromodeoxyuridine (BrdU) immunohistochemistry for assessment of human colonic cell proliferation. From 16 subjects without colonic disease biopsy specimens were collected from five different sites along the colorectum and processed for BrdU and PCNA immunohistochemistry. The mean proliferation index of PCNA was significantly higher at 133% of the value obtained with BrdU. There was, however, a good correlation between the results from both techniques (r = 0.6275; p < 0.05). Decrease in proliferation index along the colorectum was seen with both staining methods but was clearer with PCNA immunohistochemistry (caecum/ascending colon v rectum: 12.0 v 7.2; p < 0.004). The total number of crypt cells also decreased from proximal to distal (134 to 128; p < 0.06) but at no site correlated significantly with the proliferation index. It is concluded that in clinical cell kinetic studies staining for PCNA may serve as an attractive alternative to the BrdU incorporation assay.     

Changes in p53 and Waf1p21 expression and cell proliferation in esophageal carcinogenesis

AIM: To study the correlation between changes in p53 and Waf1p21 expression and cell proliferation, determined by proliferating cell nuclear antigen (PCNA), at different stages of human esophageal carcinogenesis.METHODS: Biopsied and resected esophageal tissues from a high risk population of esophageal cancer in northern China were used in this study. All specimens were fixed in 85% alcohol and processed for routine histology. The avidin biotin peroxidase complex (ABC) method was used to detect p53, Waf1p21 and PCNA.RESULTS: Strong nuclear staining of p53, Waf1p21 and PCNA was observed in normal esophageal epithelium and epithelia with different lesion severities. As the lesions progressed to dysplasia (DYS) and to esophageal squamous cell carcinoma (SCC), the Waf1p21 immunoreactivity percentage decreased. The number of Waf1p21-positive cells slightly increased from normal to basal cell hyperplasia (BCH), but did not further increase in DYS and SCC. The total number of Waf1p21-positive cells was lower than the number of p53-positive cells in normal and BCH esophageal epithelia and much lower in DYS and SCC. Waf1p21-positive cells were located in the third and fourth cell layers in half of the samples examined, which was 2-4 cell layers higher than the cells expressing PCNA and p53 in the same histological categories of normal, BCH and DYS.CONCLUSION: Low Waf1p21 levels at the DYS stage may be related to a functional loss of p53. Other mechanisms may also be responsible for the decreased Waf1p21 expression in DYS and SCC.     

Clinical significance of subcellular localization of KL-6 mucin in primary colorectal adenocarcinoma and metastatic tissues

AIM:To assess subcellular localization of KL-6 mucinand its clinicopathological significance in colorectalcarcinoma as well as metastatic lymph node and livertissues.METHODS:Colorectal carcinoma tissues as wellas metastatic lymph node and liver tissues werecollected from 82 patients who underwent colorectomyor hepatectomy.Tissues were subjected toimmunohistochemical analysis using KL-6 antibody.RESULTS:Of the 82 colorectal carcinoma patients,6showed no staining,29 showed positive staining only inthe apical membrane,and 47 showed positive stainingin the circumferential membrane and/or cytoplasm.Positive staining was not observed in non-cancerouscolorectal epithelial cells surrounding the tumor tissues.The five-year survival rate was significantly lower incases showing positive staining in the circumferentialmembrane and/or cytoplasm (63.0%) than thoseshowing positive staining only in the apical membrane(85.7%) and those showing no staining (100%).Statistical analysis between clinicopathological factorsand subcellular localization of KL-6 mucin showed thatKL-6 localization in the circumferential membrane and/or cytoplasm was significantly associated with the presenceof venous invasion (P=0.0003),lymphatic invasion(P<0.0001),lymph node metastasis(P<0.0001),liver metastasis (P=0.058),and advanced histologicalstage(P<0.0001).Positive staining was observed inall metastatic lesions tested as well as in the primarycolorectal carcinoma tissues.CONCLUSION:The subcellular staining pattern ofKL-6 in colorectal adenocarcinoma may be an importantindicator for unfavorable behaviors such as lymph nodeand liver metastasis,as well as for the prognosis ofpatients.     

狼疮肾炎患者肾组织中吲哚胺2,3-双加氧酶的表达及意义

目的检测Ⅳ型狼疮肾炎（LN）患者肾组织中吲哚胺2，3-双加氧酶（IDO）的表达情况及其与肾间质浸润炎细胞的增殖和肾小管-间质病理损害程度之间的关系。方法采用免疫组织化学染色法观察正常肾组织和Ⅳ型LN患者肾组织IDO的表达情况，并进一步分析其表达与肾间质浸润核增殖抗原（PCNA）阳性淋巴细胞数及肾小管-间质（TIL）病理损害程度之间的相关关系。结果正常肾组织未检测到IDO表达，而在Ⅳ型LN肾小管上皮细胞IDO的表达阳性，并且LN肾小管上皮细胞表达IDO的阳性强度与TIL PCNA＋浸润细胞数及TIL病理损害程度呈显著负相关。结论IDO在Ⅳ型LN肾小管上皮细胞中呈高表达，并与TIL浸润细胞增殖情况及TIL病理变化呈负相关，提示IDO可能参与LNTIL病理损害过程。     

早期胃癌组织形态,细胞核DNA含量及免疫组织化学研究

目的:对早期胃癌病理形态、细胞核DNA含量、免疫组化及治疗等进行讨论。方法:32例早期胃癌,采用S-P法免疫组化,观察p53、p21、CEA、PCNA的表达;细胞核DNA含量以及组织病理学特征。结果:早期胃癌癌周围粘膜常伴有绒毛状异型增生、腺瘤状异型增生、囊腺样异型增生、球样异型增生、灶性异型增生的形态,并与相应腺癌一致。细胞核DNA含量,异倍体细胞在6.8％～79.5 ％之间;PCNA阳性细胞数在24.7～93.2个之间;p53、p21基因蛋白和CEA阳性表达分别为37.5％、78.1％和93.8％。早期胃癌经微波治疗后,近期经手术切除的标本中75％(6/8)仍有癌细胞存在。结论:早期胃癌与癌前期异型增生的组织学形态密切相关;异倍体值、细胞增殖指数、p53、p21和CEA表达,有助于癌前病变和早期胃癌的诊断;早期胃癌以手术切除为宜。     

Detection of colorectal adenomas by routine chromoendoscopy with indigocarmine

OBJECTIVES: Nonpolypoid adenomas, which can be important precursors of colorectal cancers, are difficult to find during routine colonoscopy. The aim of this study was to evaluate the usefulness of routine chromoendoscopy in Korea, where the incidence of colorectal cancer is low compared with western countries. METHODS: Colonoscopy with chromoendoscopy was performed in 74 consecutive patients (48 men, 26 women; mean age 53.0 yr). After a careful examination of the whole colon, a defined segment of the sigmoid colon and rectum (0-30 cm from the anal verge) was stained with 20 ml of 0.2% indigocarmine solution with a spraying catheter. Nonpolypoid lesions were classified as flat or depressed types. Biopsies were taken from all lesions detected before or after staining with indigocarmine. RESULTS: Indications for colonoscopy included routine check-up (21 patients), diarrhea or loose stool (14 patients), abdominal pain (12 patients), constipation (7 patients), bleeding (6 patients), and others (14 patients). Before staining, 58 lesions were found in 30 patients (43.2%). Histology showed tubular adenoma in 41 lesions, hyperplastic or inflammatory changes in 14 lesions, adenocarcinoma in 2 lesions, and villous adenoma in 1 lesion. After indigocarmine staining for normal-looking distal 30 cm colorectal mucosa, 176 lesions were found in 46 patients (62.2%). Histologically, 158 lesions were hyperplastic or inflammatory in nature, and 17 lesions (from 11 patients) were tubular adenomas. There was one serrated adenoma. Eighteen adenomas seen only after spraying indigocarmine were 2.6 +/- 0.6 mm in diameter, and all of them were classified as flat adenomas. There was no depressed-type adenoma. No adenoma with high grade dysplasia, villous histology, or cancer was found after staining. Presence of macroscopic adenomatous lesions or carcinoma before staining could not predict the existence of adenoma after staining. CONCLUSIONS: In a large proportion of patients, flat or depressed adenomas could be found after spraying indigocarmine for normal-looking colorectal mucosa in Korea. The clinical significance of these diminutive adenomas that can be found only after spraying contrast agent needs to be further investigated.     

Inhibition of alcohol-associated colonic hyperregeneration by alpha-tocopherol in the rat

BACKGROUND: Chronic alcohol consumption results in colorectal mucosal hyperregeneration, a condition associated with an increased risk for colorectal cancer. Possible mechanisms may involve the effects of acetaldehyde and/or free radicals generated during alcohol metabolism. Vitamin E is part of the antioxidative defense system, and its concentration is decreased or its metabolic utilization increased in various tissues after chronic alcohol consumption. We wondered whether alpha-tocopherol supplementation may prevent ethanol-induced colorectal cell cycle behavior and whether these changes were related to alterations in protein synthesis. METHODS: Five groups of male Wistar rats, each consisting of 14 animals, received liquid diets as follows: group 1, alcohol; group 2, alcohol + alpha-tocopherol; group 3, control (i.e., isocaloric glucose); group 4; control (i.e., isocaloric glucose) + alpha-tocopherol. Group 5 was fed a solid chow diet ad libitum. After 4 weeks of feeding, immunohistology was performed with anti-proliferating cell nuclear antigen (PCNA) or anti-BCL2 antibodies. Fractional (k(s)) and absolute (V(s)) rates of protein synthesis and rates of protein synthesis relative to RNA (k(RNA)) and DNA (k(DNA)) were measured with a flooding dose of L-[4-3H] phenylalanine with complementary analysis of protein and nucleic acid composition. RESULTS: The PCNA index was increased significantly in the colon after ethanol administration compared with controls (ethanol, 10.3 +/- 2.3 vs. control, 6.51 +/- 1.6% PCNA positive cells, p < 0.05), although neither the protein, RNA, and DNA concentrations nor k(s), k(RNA), k(DNA), and V(s) were affected. This increase in PCNA index was significantly diminished by coadministration of alpha-tocopherol (ethanol + alpha tocopherol, 7.86 +/- 1.71% PCNA positive cells, p < 0.05) without significant alterations in protein synthetic parameters. A similar result was obtained for the PCNA index in the rectal mucosa (ethanol, 14.6 +/- 4.4 vs. control, 12.1 +/- 4.2% PCNA positive cell), although this did not reach statistical significance. Neither ethanol nor alpha tocopherol feeding had any significant effect on BCL-2 expression in the colorectal mucosa. As with the colon, protein synthetic parameters in the mucosa were not affected by alcohol feeding at 4 weeks. These effects on colonic cell turnover without corresponding changes in protein synthesis thus represent a specific localized phenomenon rather than a general increase in anabolic processes in the tissue and reaffirm the hyperregenerative properties of chronic alcohol consumption. CONCLUSIONS: Alcohol-associated hyperproliferation could be prevented, at least in part, by supplementation with alpha-tocopherol. This may support the hypothesis that free radicals are involved in the pathogenesis of alcohol-associated colorectal hyperproliferation.     

Immunohistochemical Expression of PCNA and CD34 in Colorectal Adenomas and Carcinomas Using Specified Automated Cellular Image Analysis System: A Clinicopathologic Study

Background/Aim:

To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters.

Materials and Methods:

The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 ΅m thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer).

Results:

PCNA expression was significantly increased in a sequence of normal mucosa–adenoma–carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma.

Conclusion:

PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic factor.     

Expression of proliferating cell nuclear antigen and CD44 variant exon 6 in primary tumors and corresponding lymph node metastases of colorectal carcinoma with Dukes＇＇ stage C or D

AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ stage C or D.METHODS: Formalin fixed and paraffin embedded materials of primary tumors and corresponding lymph node metastases resected from 56 patients with Dukes′ stage C or D of colorectal carcinoma were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44variant exon 6 (CD44v6).RESULTS: Thirty-one of 56 patients (55.4 %) expressed PCNA in the primary sites and 36 of 56 patients (64.3 %)expressed PCNA in the metastatic lymph nodes. A significant relation in PCNA expression was observed between the primary site and the metastatic lymph node (0.010＜P＜0.025).Forty-one of 56 patients (73.2 %) expressed CD44v6 in the primary site and 39 of 56 patients (69.6 %) expressed CD44v6 in the metastatic lymph node. There was also an significant relationship of CD44v6 between the primary site and the metastatic lymph node (0.005＜P＜0.010). No difference was observed between expression of CD44v6 and PCNA in the primary site (0.250＜P＜0.500).CONCLUSION: This study partially demonstrates that tumor cells in metastatic lymph node of colorectal carcinoma still possess cell proliferation activity and metastatic ability of tumor cells in primary site. There may be no association between cell proliferation activity and metastatic ability in colorectal carcinoma.     

幽门螺杆菌感染与老年胃癌及癌前病变PCNA、Bcl-2、p16蛋白表达的关系

目的　探讨幽门螺杆菌 ( Hp)感染老年胃癌及癌前病变患者增殖细胞核抗原 ( PCNA)、p1 6和关键性凋亡调节基因 Bcl- 2蛋白的表达。方法　免疫组化方法测定 PCNA、Bcl- 2、p1 6蛋白表达。快速尿素酶法和 HE染色检测 Hp感染。结果　从浅表性胃炎到胃癌 PCNA指数呈递增趋势 ,各组间均有显著性差异 ( P<0 .0 5)。浅表性胃炎和萎缩性胃炎组中 Hp阳性患者与 Hp阴性者的 PCNAL I相比有显著性差异 ( P<0 .0 5)。Hp阳性组肠上皮化生、异型增生组织中 Bcl- 2的阳性表达率显著高于 Hp阴性组 ( P<0 .0 5)。 p1 6在慢性胃炎中阳性表达率显著高于胃癌、肠上皮化生和异型增生 ( P<0 .0 5)。 Hp阳性萎缩性胃炎组织的 p1 6阳性表达率低于 Hp阴性组 ( P<0 .0 5)。结论　在老年胃癌发生的早期即存在 p1 6基因表达低下 ,PCNA、Bcl- 2蛋白表达增加