Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization:Analysis in western patients after curative-intent surgery

BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups.However,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further evidence.AIM To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent.Microsatellite instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by ISH.Tissue microarrays were constructed for analysis.Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification systems.RESULTS A total of 287 GC patients were included.Based on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were evidenced.Proximal location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV subtype.MSI subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)subtype.GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival(DFS)and overall survival(OS)than other subtypes.Conversely,MSI subtype of GC had better survival in both classifications.Type of gastrectomy,pT and the TCGA subtypes were independent factors associated to DFS and OS.CONCLUSION The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis,resembling the subtypes of the molecular classifications.Accordingly,this method of classification may represent a viable option for use in a clinical setting.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Clinico-pathologic significance of neuroendocrine cells in gastric carcer tissue

AIMS To elucidate the biological and clinicopathological signifi- cance of neuroendocrine(NE)cells in gastric carcinoma(GC). METHODS One hundred and eighty-nine cases of various histo- logical types of GC were observed using light microscopy, histochemistry,immunohistochemistry and electron microscopy. Of them 127 patients were followed up. RESULTS Chromogranin A(CgA)positive GC was demonstrat- ed in 85 cases(45.0%).The typos of NE cells in GC were probed using 9 kinds of hormone antibodies 49 cases(67.2%) contained more than one hormone.NE cells were found more often in poorly differentiated GC than in well differentiated ones(P<0. 01).Expression of some kinds of hormone Was relative to the dif- ferentiation and histological types of GC.BOM,CT(P<0.01) GAST and 5-HT(P<0.05)were more expressed in poorly differ- entiated cases than in well defferentiated ones.Nineteen cases of the matastatic foci in regional lymph nodes were found to have CgA positive cancer cells.The presence of HCG in matastatic lymph nodes was more often observed than that of other hormone (P<0.01).The survival rate of patients with NE positive GC was 38.9% and negative GC 52.7%.Five of 7 patients(71. 4%)with somatostatin positive GC still survived at follow up of 33-66 months,but 4 patients with HCG positive GC died in 12-29 months. CONCLUSIONS The NE cells occur more frequently in poorly differentiated GC.Certain hormones appear to be related to the metastasis and prognosis.

Classification of gastric neuroendocrine tumors and its clinicopathologic significance

AIMS To study the pathologic classification of gastric neuroendocrine tumors and its clinicopathologic significance. METHODS Paraffin embedded sections of 52 gastric neuroendocrine tumors including 42 carcinoid tumors, and 10 cases of neuroendocrine carcinoma from 326 patients who underwent resection of stomach carcinomas were studied by immunohistochemical methods including 10 endocrine markers or hormones antibodies and endocrine cells in gastric neuroendocrine tumors and extratumoral mucosa were observed under electromicroscope. RESULTS The 52 gastric neuroendocrine tumors were divided into three types: ① Gastrin dependent type of carcinoid (26 cases) accompanied by chronic atrophic gastritis (CAG) and tumor extension limited to the mucosa or submucosa complicated with hypergastrinemia and G cell hyperplasia. This type was consistently preceded by and associated with generalized proliferation of endocrine cells in the extratomoral fundic mucosa. ② Non gastrin dependent type of carcinoids (16 cases) associated with neither CAG nor hypergastrinemia. This type was more aggressive; and ③ Neuroendocrie carcinomas (10 cases), which are highly aggressive tumors. CONCLUSIONS A correct identification of different types of gastric endocrine tumors has major implications for the treatment and prognosis of the patients.

Clinicopathological significance of LRP16 protein in 336 gastric carcinoma patients

AIM： To investigate the expression of leukemia related protein 16 （LRP16）, and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients. METHODS： Immunohistochemistry was used to detect LRP16 expression in 336 cases of paraffin-embedded gastric carcinoma tissues and 60 cases of distal normal mucosa. The relationships between LRP16 expression and patients＇ age, tumor size, histological grade, clinical stage, metastatic status and prognosis were analysed. RESULTS： The expression of LRP16 was 58.6% （197/336） in gastric carcinoma and 31.7% （19/60） in distal normal gastric mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa tissues （x^2 = 14.929, P = 0.001）. LRP16 protein expression was found in 44.1% （63/143） carcinomas at stage Ⅰ and Ⅱ, and 69.4% （134/193） carcinomas at stage Ⅲ and Ⅳ （Z2 = 21.804, P = 0.001）, and in 56.9% （182/320） of cancers without metastasis but 93.8% （15/16） of those with metastasis （2 = 8.543, P = 0.003）. The expression of LRP16 was correlated with tumor size, infiltrative depth, clinical stage, lymphatic invasion and distant metastasis （all P 〈 0.05）. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of LRP16 （27.0 mo） and those without （48.0 mo, Log rank =31.644, P = 0.001）. CONCLUSION： The expression of LRP16 may be associated with invasion, metastasis and prognosis of gastric cancer.

Clinicopathologic features and immunohistochemical analysis of 67 gastric adenoma patients

Objective： The aim of this study was to investigate the clinicopathologic features of gastric adenoma. Methods： Sixty-seven cases of adenoma diagnosis of gastric biopsy specimens using light microscopy, immunohistochemistry, and follow-up methods were studied. Results： Histopathology of gastric adenoma characteristics： nuclear anaplasia, showing increase of nuclear volume and irregular, and the emergence of one or more nucleoli, mitotic ≤ 2/10 high power field （HPF）. Structural changes in the gland： adenoma of the duct much more consistent, sometimes the size of the gland and irregular contour, might be associated with intestinal metaplasia. Increased significantly when the nuclear volume, mitotic 〉 2/10 HPF, irregular gland distortion, branched structures, suggesting the development of adenomas. Immunophenotype： tumor-associated carbohydrate antigens had a higher expression; adenomatous polyposis coli gene （APC） and carcinoembryonic antigen （CEA） expression of closely related with the formation of adenoma. Mucin muc-2 high expression was negatively correlated with muc-1 low expression, the combination of both can help to determine the development and changes in gastric adenoma. Survivin, Bcl-2, p21 and p53 protein expression rare cases, four were combined with the malignant transformation of gastric adenoma was important discriminant. Ki-67 positive cells 20%-40%, and could be used as degree of cell proliferation, a reference indicator of prognosis. Thirty-six to 49 months of follow-up results showed that cured 44.8% （30/67）, there adenomatous hyperplasia 35.8% （24167）, with the development of dysplasia showed 14.4% （11/67）, the development of intramucosal carci- noma were 3.0% （2/67）. Conclusion： Gastric adenomas occur significantly increased nuclear volume, mitotic 〉 2/10 HPF, ir- regular gland distortion, branch-like structure; immunohistochemical staining showed positive expression of muc-2 decreased, muc-1 positive expression; cell proliferation index Ki -67 〉 40%; p21, p53 protein expression occurred, suggesting a tendency to cancer, endoscopic mucosal resection should be as soon as possible.

Multiple genetic alterations and behavior of cellular biology in gastric cancer and other gastric mucosal lesions:H.pylori infection,histological types and staging

AIM To investigate the expression of multiplegenes and the behavior of cellular biology ingastric cancer（GC）and other gastric mucosallesions and their relations to Helicobacter pylori（H.pylori）infection,tumor staging andhistological subtypes.METHODS Three hundred and twenty-sevenspecimens of gastric mucosa obtained viaendoscopy or surgical resection,and ABCimmunohistochemical staining were used todetect the expression of p53,p16,Bcl-2 andCOX-2 proteins.H.pylori was determined byrapid urea test combined with pathologicalstaining or14C urea breath test.Cellular image analysis was performed in 66 patients withintestinal metaplasia（IM）and/or dysplasia（Dys）.In 30 of them,both cancer and theparacancerous tissues were obtained at the timeof surgery.Histological pattern,tumor staging,lymph node metastasis,grading ofdifferentiation and other clinical data werestudied in the medical records.RESULTS p16 expression of IM or Dys wassignificantly lower in positive H.pylori chronicatrophic gastritis（CAG）than those withnegative H.pylori（CAG:54.8% vs 88.0%,IM:34.4% vs 69.6%,Dys:23.8% vs 53.6%,allP【0.05）,Bcl-2 or COX-2 expression of IM orDys in positive H.pylori cases was significantlyhigher than that without H.pylori（Bcl-2:68.8%vs23.9%,90.5% vs 60.7%;COX-2:50.0% vs10.8%,61.8% vs 17.8%;all P【0.05）.Themean number of most parameters of cellularimage analysis in positive H.pylori group wassignificantly higher than that in negative H.pylori group（Ellipser:53±14,40±12μm,Area1:748±572,302±202 μm2,Area2:3050±1661,1681±1990 μm2,all P【0.05;Ellipseb:79±23,58±15 μm,Ratio1:22%±5%,13%±4%,Ratio2:79%±17%,53%±20%,all P【0.01）.There was significant correlation between Bcl-2and histologic pattern of gastric carcinoma,andbetween COX-2 and tumor staging or lymph nodemetastasis（Bcl-2:75.0% vs 16.7%;COX-2:76.0% vs 20.0%,79.2% vs 16.7%;allP【0.05）.CONCLUSION p1l6, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/ progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infection. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.

Expression and significance of proapoptotic gene Bax in gastric carcinoma

AIM To study the expression of proapoptotic gene Bax in human gastric carcinoma and its significance. METHODS Using immunohistochemistry methods, the Bax protein expression in 57 specimens of gastric carcinoma and its relationship with clinical status and pathomorphological parameters were observed. RESULTS Thirty three (57 89%) cases were positive for Bax protein staining which was mainly located in the cytoplasm of tumor cells. The rate of Bax protein expression was not correlated with the tumor size, lymph node metastasis, depth of invasion, clinical stages of tumors and age and sex of patients ( P >0 05), but strongly associated with the morphological type and differentiation degree of tumors. It was significantly higher in intestinal type and well/moderately differentiated gastric carcinoma than in diffuse type and poorly differentiated gastric carcinoma ( P <0 05 and P <0 01). CONCLUSION The proapoptotic gene Bax is differentially expressed in most of gastric carcinoma and may take part in the modulation of apoptosis in gastric carcinoma. The expression of Bax might be associated with the occurrence of intestinal type gastric carcinoma and the differentiation of gastric carcinoma.

Clinical significance of Fas antigen expression in gastric carcinoma

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胃底腺黏膜型腺癌4例临床病理特征

目的观察胃底腺黏膜型腺癌(gastric adenocarcinoma of fundic-gland mucosa type,GA-FGM)的临床病理学特征。方法回顾性分析4例GA-FGM的临床病理资料,采用免疫组化EnVision法检测黏蛋白(MUC5AC、MUC6)表达,并复习相关文献。结果肿瘤向胃小凹上皮和胃底腺两种方向分化。胃小凹上皮分化部分由低度异型的高柱状肿瘤性上皮构成,可呈乳头状、绒毛状或管状形态,免疫组化标记MUC5AC阳性;胃底腺分化成分表现为向颈黏液细胞、主细胞和壁细胞分化,免疫组化标记MUC6阳性。结论GA-FGM具有独特的形态学特征,活检诊断困难,与胃底腺型腺癌形态学有重叠又有不同,需加强认识,免疫组化在鉴别诊断中起重要作用。

Relationship between expression of laminin and pathological features in human colorectal carcinoma

AIM To study the expression and significance of laminin in human colorectal carcinoma. METHODS Using the monoclonal antibody to laminin and streptavidin peroxidase immunohistochemical method, the expression of laminin in 63 cases of human colorectal carcinoma tissues was determined. RESULTS In normal large intestinal mucosa adjacent to carcinoma, laminin was largely restricted to basement membrane in continuous linear pattern. In contrast, human colorectal carcinomas exhibited a progressive loss of an intact basement membrane that was correlated with decreasing differentiation degree. Well and moderately differentiated tumors exhibited a thin basement membrane with intermittent disruptions, and poorly differentiated tumors exhibited no areas of intact basement membrane. An association was found between lack of basement membrane laminin immunohistochemical staining in colorectal carcinoma and poorly differentiated tumor ( P <0 01) . CONCLUSION Immunohistochemical staining for laminin could provide a very useful index for the determination of the differentiation degree of colorectal carcinoma.

腹腔镜胃癌根治性切除标本cyclin D1和SLeX表达的临床病理研究

目的探讨腹腔镜胃癌根治性切除标本cyclin D1和SLeX表达与患者临床病理特征及预后的关系。方法85例腹腔镜胃癌根治性手术切除标本及30例癌旁胃组织,应用免疫组织化学染色EliVision^(TM)plus二步法检测cyclin D1和SLeX在胃癌及癌旁胃组织中的表达,分析cyclin D1和SLeX与患者性别、癌灶大小、分化程度、临床分期、转移浸润及5年生存期6项临床病理特征的相关性。结果癌组织cyclin D1和SLeX阳性率分别为61.2%(52/85)和85.9%(73/85),癌旁胃组织cyclin D1和SLeX阳性率分别为0和6.7%(2/30),差异均有统计学意义(P<0.05)。Cyclin D1和SLeX表达与性别及癌灶大小无关(P>0.05),在低分化、进展期、有转移浸润和5年内死亡患者中,Cyclin D1和SLeX阳性率均显著高于(高+中)分化、早期、无转移浸润和5年内生存患者(P<0.05)。Cyclin D1和SLeX表达呈正相关(r=0.40)。结论Cyclin D1和SLeX与胃癌发生发展显著相关,两者共阳性表达预示胃癌分化程度低、进展快、易浸润转移、生存期短。

Human epidermal growth factor receptor 2 expression in mixed gastric carcinoma

AIM: To investigate human epidermal growth factor receptor 2(HER2) amplification and protein expression in mixed gastric carcinoma.METHODS: Fluorescence in situ hybridization and immunohistochemistry were used to detect HER2 amplification and protein expression in 277 cases of mixed gastric carcinoma. Protein staining intensity was rate as 1+, 2+, or 3+.RESULTS: Of the 277 cases, 114(41.2%) expressed HER2 protein. HER2 3+ staining was observed in 28/277(10.1%) cases, 2+ in 37/277(13.4%) cases, and 1+ in 49/277(17.7%) cases. A HER2 amplification rate of 17% was detected, of which 25/28(89.3%) were observed in the HER2 3+ staining group, 17/37(45.9%) in 2+, and 5/49(10.2%) in 1+. Of the 47 patients with HER2 amplification who received chemotherapy plus trastuzumab, 22 demonstrated median progression-free and overall survivals of 9.1 mo and 16.7 mo, respectively, which were significantly better than those achieved with chemotherapy alone(5.6 mo and 12.1 mo, respectively) in 19 previously treated patients(P s < 0.05). CONCLUSION: HER2 detection in mixed gastric carcinoma displays high heterogeneity. Relativelyquantitative parameters are needed for assessing the level of HER2 amplification and protein expression.

Gastric-and intestinal-type marker expression in invasive ductal adenocarcinoma of the pancreas

BACKGROUND:Although invasive ductal adenocarcinoma of the pancreas(PDAC) manifests as a relatively uniform histomorphological feature of the pancreatobiliary type,it may be complicated by metaplastic changes and heterogeneous gastric and intestinal elements.This study aimed to investigate the complication rate and clinicopathological significance of such heterogeneous elements.METHODS:Fifty-nine patients who underwent resection of PDAC were examined in this study.Immunohistochemically,tumors showing high expression(>25%) of the intestinal-type(INT) marker CDX2 were classified as PDAC with INT.Those with high expression(>25%) of the gastric-type(GAS) marker MUC5AC were classified as PDAC with GAS,while those with high expression of both markers were classified as PDAC with INT/GAS.These patients were compared with those with PDAC of the negative group in which neither markers was highly expressed to examine their clinicopathological significance.RESULTS:In the 59 patients,31(52.5%) showed high CDX2 or MUC5AC expression.Twenty-eight patients(47.5%) belonged to a negative group,11(18.6%) to a PDAC with INT group,15(25.4%) to a PDAC with GAS group,and 5(8.5%) to a PDAC with INT/GAS group.No significant differences were observed for age,gender,size,localization,T classification,or prognosis among the four groups.Although the PDAC with GAS group had well differentiated types significantly more than the other groups,the rate of lymph node metastasis in this group was significantly higher(PDAC with GAS:73%;other groups:36%).CONCLUSION:Complications with heterogeneous elements are not uncommon in PDAC,and this should be considered during the diagnosis and treatment of PDAC along with histogenesis of the disease.

胃肿瘤标志物对胃癌新辅助治疗后病理完全缓解的预测价值

目的:探究局部进展期胃癌(locally advanced gastric cancer,LAGC)新辅助治疗后病理完全缓解(pathological complete response,pCR)的影响因素,评估胃肿瘤标志物在LAGC患者pCR的预测价值。方法:回顾性分析2020年1月至2024年4月期间于中国人民解放军总医院第一医学中心接受新辅助治疗后行胃癌根治术及胃肿瘤标志物检查的213例患者临床与病理资料,其中pCR组20例,非pCR组193例。比较pCR与胃肿瘤标志物、临床病理特征的相互关系,探究pCR的独立预测因素,并构建诺曼图预测模型。结果:213例患者中,20例(9.4%)患者术后病理结果提示pCR。单因素分析结果显示,年龄(P=0.067)、肿瘤瘤床直径(P<0.001)、胃泌素-17(P=0.005)、CA72-4(P=0.073)、胃蛋白酶原比值(PG1/PG2)(P=0.024)及新辅助免疫治疗(P=0.022)与LAGC患者新辅助治疗后pCR显著性相关(P<0.1)。将上述指标纳入多因素分析,表明新辅助免疫治疗、CA72-4<2.5 U/mL、胃泌素-17<1.48 pmol/L、肿瘤瘤床直径<2.85 cm是LAGC患者pCR的独立影响因素(P<0.05)。依托多因素指标构建诺曼图预测模型并绘制受试者工作特征曲线(receiver operating characteristic curve,ROC),AUC(95%CI)为0.863(0.785~0.942)。校准曲线及临床决策曲线提示诺曼图校准良好且具有较好的净收益。结论:胃肿瘤标志物可有效预测LAGC患者新辅助治疗后pCR,以胃肿瘤标志物为基础构建的诺曼图具有良好的预测能力,可为临床决策提供参考。

糖皮质激素受体在乳腺癌中的表达及临床意义

目的探讨乳腺癌组织中糖皮质激素受体(GR)的表达及临床意义。方法选取2021年7月至2023年6月于中国人民解放军联勤保障部队第九六〇医院行手术治疗的140例女性乳腺癌石蜡标本,采用免疫组化方法检测乳腺癌组织及癌旁组织中GR的表达,并应用χ^(2)检验、Fisher精确概率法以及Kruskal-Wallis秩和检验分析其与临床病理特征以及不同分子分型的关系。结果乳腺癌组织中GR蛋白阳性率高于癌旁组织阳性率(P<0.05)。组织学Ⅰ级GR阳性率高于Ⅱ级和Ⅲ级,GR阳性率与组织学分级呈负相关。TNM分期Ⅲ期GR阳性率高于Ⅱ期和Ⅰ期,GR阳性率与TNM分期呈正相关。发生淋巴结转移患者GR阳性率高于未发生转移患者。肿瘤直径>2 cm患者GR阳性率高于肿瘤直径≤2 cm患者,差异均有统计学意义(P<0.05)。ER阳性肿瘤GR阳性率高于ER阴性肿瘤,人表皮生长因子受体-2(HER-2)阴性肿瘤GR阳性率高于HER-2阳性肿瘤。GR表达在乳腺癌不同分子分型中存在明显差异,Luminal A型GR阳性率最高,其次是Luminal B型和三阴性乳腺癌(TNBC),少见于Her-2过表达型,差异有统计学意义(P<0.05)。患者年龄、月经、PR和Ki-67与GR表达均无明显相关性(P>0.05)。结论GR在乳腺癌组织中高表达,并与多种临床病理特征存在相关性,提示GR可能是一个潜在的乳腺癌进展预判指标和治疗的新靶点。

Immunohistochemical detection of ras p21 expression in pancreatic adenocarcinoma and its clinicopathological significance

By using anti-ras p21 mouse monoclonal antibody(McAb),SCI-oncogema 1,the au-thors examined immunohistochemical staining in pancreatic adenocarcinoma.The percentage ofpositive staining was 55.8%(24/43)and was related to either histopathological grade or clinicalstage.Upon statistical analysis of the correlation between the positive staining of anti-ras p21and patient prognosis with Klaplan-Meier curve and Log-rant test,the positive staining casesshowed comparatively better prognosis than the negative ones,suggesting that ras p21 expres-sion may be important in the early stage of pancreatic carcinoma.

组蛋白乙酰转移酶P300和去乙酰化酶SIRT2在乳腺浸润性导管癌中的表达

目的 探讨乳腺浸润性导管癌中组蛋白乙酰转移酶P300(P300)和去乙酰化酶SIRT2(SIRT2)的表达及其与临床病理特征的关系。方法 选取385例乳腺浸润性导管癌组织为病例组,36例癌旁组织为对照组,制成组织芯片,采用免疫组化En Vision二步法检测两组中P300和SIRT2的蛋白表达水平并比较其表达差异;分析病例组中P300和SIRT2蛋白水平与患者临床病理特征的关系,采用Spearman法分析乳腺癌患者中P300和SIRT2蛋白的相关性;采用Kaplan-Meier和Log rank test统计学方法分析P300和SIRT2蛋白与乳腺癌患者预后的关系。结果 病例组P300蛋白低表达率高于对照组、SIRT2蛋白低表达率低于对照组,差异有统计学意义(P<0.05);乳腺癌组织中,P300蛋白在肿瘤最大径>5 cm的低表达率高于≤5 cm、在TNM分期Ⅲ~Ⅳ期的低表达率高于Ⅰ~Ⅱ期、在有淋巴结转移的低表达率高于无淋巴结转移、在Ki67高表达的低表达率高于Ki67低表达、在LuminalB型中的低表达率高于三阴性乳腺癌(TNBC),差异有统计学意义(P<0.05);SIRT2蛋白在组织学分级3级中的低表达率低于1~2级、在肿瘤最大径>5 cm的低表达率高于≤5 cm、在Ki67高表达的低表达率低于Ki67低表达、在LuminalA型和LuminalB型中的低表达率低于HER2阳性型和TNBC,差异有统计学意义(P<0.05);P300和SIRT2蛋白的表达呈负相关(r=-1.77,P<0.001);P300蛋白低表达比高表达总体无病生存率低(P=0.046)。结论 P300和SIRT2蛋白可能与乳腺浸润性导管癌的发生、发展相关,P300蛋白低表达可能提示乳腺浸润性导管癌患者预后较差。

Expression profiles of gastric cancer molecular subtypes in remnant tumors

BACKGROUND Remnant gastric cancer(RGC)is a carcinoma arising in the stomach remnant after previous gastric resection.It is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer(PGC).However,as it is less frequent,its profile regarding the current molecular classifications of gastric cancer has not been evaluated.AIM To evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and in situ hybridization to determine whether the expression profile is different between PGC and RGC.METHODS Consecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels:Epstein-Barr virus in situ hybridization,immunohistochemistry for mismatch repair proteins(MutL homolog 1,MutS homolog 2,MutS homolog 6,and PMS1 homolog 2),p53 protein,and E-cadherin expression.Clinicopathological characteristics and survival of these patients were compared to 284 PGC patients.RESULTS A total of 40 RGC patients were enrolled in this study.Compared to PGC,older age(P<0.001),male(P<0.001),lower body mass index(P=0.010),and lower hemoglobin level(P<0.001)were associated with RGC patients.No difference was observed regarding Lauren’s type and pathologic Tumor Node Metastasis stage between the groups.Regarding the profiles evaluated,EBV-positive tumors were higher in RGC compared to PGC(P=0.039).The frequency of microsatellite instability,aberrant p53 immunostaining,and loss of E-cadherin expression were similar between RGC and PGC.Higher rates of simultaneous alterations in two or more profiles were observed in RGC compared to PGC(P<0.001).According to the molecular classification,the subtypes were defined as EBV in nine(22.5%)cases,microsatellite instability in nine(22.5%)cases,genomically stable in one(2.5%)case,and chromosomal instability in 21(52.5%)cases.There was no significant difference in survival between molecular subtypes in RGC patients.CONCLUSION RGC was associated with EBV positivity and higher rates of co-altered expression profiles compared to PGC.According to the molecular classification,there was no significant difference in survival between the subtypes of RGC.

进展期胃癌术后生存相关影响因素分析

目的:探讨进展期胃癌外科手术后生存预后的影响因素。方法:采用回顾性病例系列研究方法,纳入577例行胃癌根治术的cⅡ~ⅣA期胃癌病人。分析临床特征、手术方式、病理特征、辅助化疗等对病人术后无疾病生存期(DFS)和总体生存期(OS)的影响。结果:577例进展期胃癌病例的中位DFS为48个月,中位OS为53个月,病例中出现转移及复发294例,死亡302例,275例存活。Kaplan-Meier生存分析显示,年龄、肿瘤部位、肿瘤直径、Borrmann分型、分化程度、淋巴结转移、神经脉管侵犯、浸润深度、临床分期、是否化疗、化疗周期、人表皮生长因子2(HER2)是否阳性、Ki-67是否阳性是胃癌预后的相关因素,与胃癌的DFS及OS相关(P<0.05~P<0.01)。Cox回归比例风险模型分析显示,Borrmann分型、淋巴结转移、浸润深度、化疗周期、HER2及Ki-67是DFS的独立预后因素(P<0.05~P<0.01),Borrmann分型、淋巴结转移、浸润深度、化疗周期、HER2是OS的独立预后因素(P<0.05~P<0.01)。HER2阳性、Ki-67阳性的复发危险分别为阴性的1.868倍、1.665倍,HER2阳性的死亡危险是阴性的1.832倍。结论:手术方式、病理特征及辅助化疗对进展期胃癌DFS及OS均有影响。