垂体促甲状腺激素腺瘤中SSTR表达谱及全数字切片自动图像分析的探索性研究

  目的  探索垂体促甲状腺激素（thyroid stimulating hormone,TSH）腺瘤中生长抑素受体（somatostatin receptor,SSTR）的表达以及全数字切片自动图像分析技术的应用。  方法  分析2013年1月至2019年12月北京协和医院的37例垂体TSH腺瘤的石蜡包埋组织标本及临床病理资料,利用各型SSTR1-SSTR5抗体进行免疫组织化学染色,分别进行人工判读和全数字切片自动图像分析,比较各型SSTR表达与性别、年龄、肿瘤大小、Ki-67指数以及侵袭的相关性,并对比人工判读和软件自动分析的一致性。   结果  垂体TSH腺瘤中SSTR1、SSTR2、SSTR4和SSTR5多为2分和3分表达,其中3分占比均超过50.0%（4型SSTR占比依次分别为59.5%、78.4%、64.9%和56.8%）。SSTR1表达与侵袭呈明显负相关（人工r=-0.417,P=0.010;软件r=-0.406,P=0.013）,并与SSTR2表达具有显著相关性（人工r=0.420,P=0.010;软件r=0.338,P=0.040）。各型SSTR表达的人工判读与图像自动分析结果均显示了较好的一致性。  结论  垂体TSH腺瘤肿瘤组织中SSTR1、SSTR2、SSTR4和SSTR5均有较高水平的表达,利用基于数字化全切片的图像自动分析技术可获得与病理医师人工判读相近的评估效果。     

Somatostatin Receptor 2 and 5 Expressions in Gastroenteropancreatic Neuroendocrine Tumors in Turkey

Background: Gastroenteropancreatic neuroendocrine tumors (GNs) are slow growing and although theirincidence has increased in recent years, they are relatively rarely seen. Somatostatin analogues are used inthe treatment of GNs that express somatostatin receptor (SR). We aimed to investigate the expression ofSR2 and SR5 in GNs. Materials and Methods: In this study the expression of SR2 and SR5 was investigatedimmunohistochemically in 49 cases (26 males, 23 females) diagnosed and graded with GN according to the WorldHealth Organization classification 2010. Results: The percentage of SR2 staining was 91.0% in grade 1, 82.8%in grade 2 and 100% in grade 3. On the other hand, the percentage of SR5 staining was 81.8% % in grade 1,60.0% in grade 2 and 0% in grade 3. According to the tumor localization, the percentages of SR2 expressionwere as follows: pancreas 85.7%, stomach 100%, small bowel 70%, appendix 85.7% and rectum 100%. Thepercentages of SR5 expression were: pancreas 61,9%, stomach 37.5%, small bowel 70%, appendix 71.5%and rectum 66.6%. There was a significant negative correlation between ki67 percentage and SR5 expression(r=-0.341, p=0.016). Conclusions: In this study, GNs were found to highly express SR2 and SR5. Although theexpression of SR2 and SR5 changed according to tumor localization, the expression of SR2 was higher than theexpression of SR5 in GN. There was a significant negative correlation between ki67 and SR5. Accordingly, SR5may be a prognostic indicator of GN.     

胃癌的雌孕激素受体检测及应用三苯氧胺治疗的研究

目的　探讨胃癌的雌激素受体 (ER)、孕激素受体 (PR)表达情况及其对预后的影响 ,观察三苯氧胺 (TAM)在胃癌治疗中的作用。方法　从 1993年 2月到 2 0 0 0年 12月 ,用免疫组化SP法 ,对 12 3例胃癌术后标本进行了ER、PR检测 ,并将TAM应用于胃癌的内分泌治疗 ,追踪随访 5年。结果　①胃癌的ER、PR阳性率均为 36 5 9% ( 45 / 12 3) ;②分化好 (高、中分化 )的胃癌ER、PR阳性率18.5 7% ( 13/ 70 ) ,分化差 (低分化腺癌 ,粘液腺癌和印戒细胞癌 )的胃癌ER、PR阳性率 60 38% ( 32 / 5 3) ,统计学处理有显著差异 (P <0 .0 5 ) ;③ER、PR阳性表达与临床分期呈正相关 ,分期越晚阳性率越高 ,但统计学无显著差异 (P >0 .0 5 ) ;④接受化疗 34例 ,化疗同时辅以TAM内分泌治疗 31例 ,5年生存率分别为 2 6.47% ( 9/ 34 )、5 1.61% ( 16/ 31) ,二者有显著差异 (P <0 .0 5 )。结论　本研究表明 ,ER、PR阳性表达的胃癌是一种雌、孕激素依赖性肿瘤 ,化疗联合TAM内分泌治疗 ,可抑制胃癌细胞的生长 ,提高 5年生存率     

胃癌109例雌激素受体与孕激素受体的检测研究

自１９８６～１９９３年采用李氏荧光雌激素组织化学法对胃癌１０９创作了雌激素受体（ＥＲ）、孕激素受体（ＰｇＲ）测定，同时对８例非肿瘤病人的胃正常粘膜作了ＥＲ、ＰｇＲ测定。１０９例胃癌的ＥＲ、ＰｇＲ阳性率分别为２３％、２７．５％，８例非肿瘤病人的胃正常粘膜ＥＲ、ＰｇＲ均阴性。１０９例胃癌中高分化腺癌ＥＲ、ＰｇＲ阳性率分别为４４．１％（１５／３４）、４７．１％（１６／３４），均明显高于低分化腺癌的１４％（６／４３）及２０．９％（９／４３），ＥＲ为Ｐ＜０．０２、ＰｇＲ为Ｐ＜０．０５，发病年龄及性别与ＥＲ、ＰｇＲ均无关。认为ＥＲ、ＰｇＲ阳性的胃癌与雌激素靶器官的恶性肿瘤一样，可能为雌激素依赖性肿瘤，对内分泌治疗有着良好的前景。     

子宫内膜样腺癌组织中内分泌细胞及其雌、孕激素受体的研究

目的　探讨子宫内膜样腺癌组织中内分泌细胞与雌、孕激素受体的关系。方法　采用免疫组化S -P法 ,检测 5 0例子宫内膜样腺癌组织中嗜铬素A(CgA )、雌激素受体 (ER )及孕激素受体 (PR )的表达情况 ,并对CgA阳性的子宫内膜样腺癌组织分别进行CgA /ER及CgA/PR双重免疫组化染色。 结果　子宫内膜样腺癌组织中CgA阳性率为 44 .0 % (2 2 /5 0 )。ER阳性率为2 8.0 % (14 /5 0 ) ,PR阳性率为 5 0 .0 % (2 5 /5 0 )。子宫内膜样腺癌CgA阳性组与阴性组之间ER表达率无显著性差异 (P >0 .0 5 ) ,但PR表达率有显著性差异 (P <0 .0 5 )。 2 2例CgA阳性子宫内膜癌细胞中CgA /ER同时表达率为 10 .1% (2 2 1/2 2 0 8个细胞 ) ,CgA/PR同时表达率为 2 0 .1% (4 90 /2 44 0个细胞 )。结论　子宫内膜癌组织出现较多的内分泌细胞及ER、PR的缺失是肿瘤异质性的表现。内分泌细胞不仅影响肿瘤细胞的生长 ,而且可能与子宫内膜癌对激素治疗的抗性或激素治疗后的复发有关     

Helicobacter bilis in Human Gallbladder Cancer: Results of aCase-control Study and a Meta-analysis

Introduction: Gallbladder cancer is an uncommon neoplasm of uncertain etiology and poor survival.Recently, interest has been generated in bacterial infections and cancers. Helicobacter is one such bacteriumfound to be associated with gastric MALToma, gastric adenocarcinoma and hepatobiliary neoplasms. Patientsand methods: Fifty four gallbladder cancer and 55 controls with cholelithiasis were studied. Helicobacter biliswas identified using 16S rRNA PCR. Relative risk and odds ratio with 95% CI were estimated. A detailed searchof literature was carried out and selected relevant articles were extracted. A meta analysis was carried outusing a random effect model. Results: Helicobacter bilis was identified in 32/54 patients and 32/55 controls, Therelative risk of gallbladder cancer in H. bilis positive cases was 1.05 (95% CI 0.49 to 2.24). Of the 10 identifiedcase control studies on Helicobacter in the hepatobiliary tract 3 each were on gallbladder cancer and H. bilis. Inmeta analysis a pooled odds ratio of 4.13 (95% CI 2.68-6.36) favoring Helicobacter was observed. Pooled analysisof published studies on gallbladder cancer showed an odds ratio of 1.24 (95% CI 0.63-2.44). Conclusions: Thepresent study failed to demonstrate any increase in risk of gallbladder cancer in presence of Helicobacter bilis.It may be hypothesized that increased risk observed in earlier studies may be indirectly due to increase in therisk of gallstones, although lack of any study specifically looking at this aspect and absence of normal controlsin the present study makes this assumption superfluous.     

Roles of Salmonella typhi and Salmonella paratyphi in Gallbladder Cancer Development

Background: Typhoid (Salmonella typhi and paratyphi) carriers and gall bladder cancer (GBC) are endemic in northern India. Results of previous studies about association of typhoid carriers with GBC are inconsistent. We studied antibodies against Salmonella typhi and paratyphi in serum samples of patients with GBC. Methods: We performed modified Widal test for antibodies against Salmonella typhi (Vi and O) and Salmonella paratyphi (AO and BO) antigens in patients with GBC (n=100), xanthogranulomatous cholecystitis (XGC, n=24), chronic cholecystitis (CC, n=200) and healthy controls (HC, n=200). Results: Serum antibodies against Salmonella were more frequently positive in GBC (22%) and XGC (29%), particularly in males in age ≥50 years (GBC: 47% and XGC: 50%) vs. HC (0) (p <0.01). Vi antibody was more common in GBC (13%, OR:9.8) and XGC (8%, OR:5.9) than HC (2%). O antibody was more common in GBC (8%, OR: 8.6) and XGC (8%, OR: 9.0) than HC (1%). O antibody was also more common in males with GBC (12%) than CC (1%) and HC (1%) (P=0.02 and p <0.001, respectively). AO (6%) and BO (4%) antibodies were detected in GBC, particularly in males, than HC (0), (p <0.01). Salmonella antibodies were more frequent in GBC with GS than those without GS (50% vs. 20%, OR=3.94, P=0.01). Conclusions: Salmonella carrier state was more common in GBC and XGC, particularly in elderly males than HC. The Vi antibody was more common in GBC and XGC than HC. Salmonella infection was more common in GBC with GS than those without GS.     

Expression and Clinical Significance of Sushi Domain- Containing Protein 3 (SUSD3) and Insulin-like Growth Factor-I Receptor (IGF-IR) in Breast Cancer

Background: To investigate the expression of insulin-like growth factor-I receptor (IGF-IR) and sushi domaincontaining protein 3 (SUSD3) in breast cancer tissue, and analyze their relationship with clinical parameters and the correlation betweenthe two proteins. Materials and Methods: The expression of IGF-IR and SUSD3 in 100 cases of breast cancer tissues and adjacent normal breast tissues after surgery was detected by immunohistochemical technique MaxVisionTM, and the relationship with clinical pathological features was further analyzed. Results: The positive rate of IGF-IR protein was 86.0% in breast cancer, higher than 3.0% in adjacent normalbreast tissue (P<0.05) .The positive expression rate of SUSD3 protein was 78.0% in breast cancer, higher than 2.0% in adjacent normal breast tissue (P<0.05). The expression of IGF-IR and SUSD3 was related to estrogen receptor and pathological types (P<0.05),but not with age, stage, the expression of HER-2 and Ki-67 (P>0. 05). The expression of IGF-IR and SUSD3 in breast cancer tissue was positively related (r= 0.553, P<0.01). Conclusions: The expression of IGF-IR and SUSD3 may be correlated to the occurrence and development of breast cancer. The combined detection of IGF-IR, SUSD3 and ER may play an important role in judging prognosis and guiding adjuvant therapy after surgery of breast cancer.     

生长抑素受体在复发和转移性乳腺癌组织中的表达及意义

目的 探讨生长抑素受体(SSTR)在复发和转移性乳腺癌组织中的表达及意义.方法 采用免疫组化法检测86例复发和转移性乳腺癌切除转移病灶、转移灶旁组织和正常组织中的SSTR,比较分析3组表达情况;同时将检测结果与这86例患者第1次术后的SSTR表达情况进行比较.结果 局部复发癌组织、转移淋巴结组织中SSTR的阳性表达率分...     

Analysis of Cytosol CA15-3, Carcinoembryonic Antigen, Estrogen and Progesterone Receptors in Breast Cancer Tissues

Cytosol levels of carcinoembryonic antigen (CEA), CA15-3, estrogen receptor (ER) and progesterone receptor (PgR) of 194- primary breast cancer tissues were measured. ER and PgR determined by enzyme immunoassay methods correlated inversely with Page's grades of histological atypia and mitotic rate. Cytosol CA15-3 correlated inversely with the grades of tubular and nuclear atypia and positively with the mitotic rate. CA15-3 correlated positively with ER and PgR. Cytosol CEA showed no correlation with the pathological grade or hormone receptor status. These results indicate that hormone receptor-positive breast cancers tend to have more differentiated morphology and slower growth rate than those without those receptors and that the cytosol CA15-3 level may reflect some of the intrinsic malignant potency, particularly the growth rate, of breast cancer. Cytosol CA15-3 as well as the hormone receptor status may have prognostic value for patients with breast cancer.     

卵巢肿瘤性类固醇激素受体的研究

采用Ｌｅｅ ＳＨ荧光素组化法检测８０例卵上皮源性肿瘤的雌激素受体（ＤＲ）和孕激素受体（ＰＲ）。结果发现：４０例良性肿瘤中，２７例有中、高水平的ＥＲ、ＰＲ（６９％）。３８例卵巢癌中，１６例有中、高水平的ＥＲ、ＰＲ（４１％）。未见全部由受体阴性癌细胞构成的肿瘤。卵巢交界性肿瘤的ＥＲ、ＰＲ阳性细胞多位于相对良性区域、随着肿瘤异型性的增加，ＥＲ、ＰＲ阳性细胞减少。高分化癌较中、低分化癌的受体水平高。临床早     

Aflatoxin Contamination of Red Chili Pepper From Bolivia and Peru,Countries with High Gallbladder Cancer Incidence Rates

Chilean red chili peppers contaminated with aflatoxins were reported in a previous study. If the developmentof gallbladder cancer (GBC) in Chile is associated with a high level of consumption of aflatoxin-contaminated redchili peppers, such peppers from other countries having a high GBC incidence rate may also be contaminatedwith aflatoxins. We aimed to determine whether this might be the case for red chili peppers from Bolivia andPeru. A total of 7 samples (3 from Bolivia, 4 from Peru) and 3 controls (2 from China, 1 from Japan) wereevaluated. Aflatoxins were extracted with acetonitrile:water (9:1, v/v) and eluted through an immuno-affinitycolumn. The concentrations of aflatoxins B1, B2, G1, and G2 were measured using high-performance liquidchromatography (HPLC), and then the detected aflatoxins were identified using HPLC-mass spectrometry. Insome but not all of the samples from Bolivia and Peru, aflatoxin B1 or aflatoxins B1 and B2 were detected. Inparticular, aflatoxin B1 or total aflatoxin concentrations in a Bolivian samples were above the maximum levels foraflatoxins in spices proposed by the European Commission. Red chili peppers from Bolivia and Peru consumedby populations having high GBC incidence rates would appear to be contaminated with aflatoxins. These datasuggest the possibility that a high level of consumption of aflatoxin-contaminated red chili peppers is related tothe development of GBC, and the association between the two should be confirmed by a case-control study.     

12种凝集素与雌激素和孕激素受体在乳腺癌中的对比研究

本文应用亲和组化法对100例乳腺癌的12种凝集素受体与ER和PR进行对比研究,结果发现:(1)PNA-R与ER阳性符合率91.2％;RCA-R与PR为88.5％。(2)PNA-R与ER,RCA-R与PR在乳腺癌各年龄组、月经状况、肿瘤大小、淋巴结转移和各组织学类型的阳性率呈正相关。(3)PNA-R、ER、RCA-R、PR阳性患者肿瘤的复发率低于阴性患者(P<0.05)。结果提示乳腺癌PNA-R与ER,RCA-R与PR有一致性,可通过亲和组化法对常规石蜡切片测定乳腺癌PNA-R和RCA-R,以推测乳腺癌患者的ER和PR状况,对指导临床估计预后和内分泌治疗有重要意义。     

Expressional Correlation of Human Epidermal Growth Factor Receptor 2, Estrogen/Progesterone Receptor and Protein 53 in Breast Cancer

Background: This study aimed to show the localization of estrogen / progesterone receptors, human epidermalgrowth factor receptor 2 (Her-2) and protein 53 (p53) by immunohistochemistry in a series of consecutive breastcancer patients. Materials and Methods: The study covered invasive breast cancers from 299 patients presentingat the Oncogenetic Clinic and Pathology Centers of Ahwaz Jondishapour University of Medical Sciences Hospitalin Iran during the time period from 2009 to 2011. The Scarff-Bloom Richardson scoring method was used. Results:Of the 299, 27% (80/299) were <40, 33% (100/299) were 41-50, and the remaining 40% (119/299) were>50 yearsold. The highest incidence of breast cancer in this study population was in the group of more than 50 year age,and the most common histological type of breast cancer was the invasive ductal carcinoma, which accountedfor 68% (203/299) of the cases. Out of possible total of 207, 6% (13/207), 41% (85/207), and 53% (109/207) werescored as grade І, ІІ, ІІІ, respectively. Conclusion: Our findings demonstrated a lack of association betweenlabeling for the markers studied and tumor size and age of the patients. We confirmed an association betweenER labeling and nuclear grade of breast cancer. The conflicting results obtained compared with the literature bebecause of differences in the immunohistochemical techniques applied in the various studies and to the scoringsystems used.     

三氧化二砷重新激活PC-3前列腺癌细胞雄激素受体基因的表达

目的探讨三氧化二砷（As2O3）重新激活PC-3前列腺癌细胞雄激素受体（AR）基因的表达。方法用免疫组织化学的方法，对用浓度为2mg／L的As2O3处理前后的PC-3前列腺癌细胞和阳性对照的LNCaP前列腺癌细胞（AR）基因的表达情况进行检测分析。结果As2O3处理过的PC-3前列腺癌细胞AR的阳性表达率明显增高（P〈0．05）。结论As2O3可以重新激活PC-3前列腺癌细胞（AR）基因的表达。     

Prognostic Significances of Estrogen and Progesterone Receptors in Primary Operable Breast Cancer

Both estrogen and progesterone receptors have been determinedin 613 primary breast cancer patients treated by radical mastectomy.At the cut-off value of 5 fentomoles (fmol) cytosol pro-tein/mgfor both receptors, patients with estrogen or progesterone receptor-positivebreast cancer showed significantly favorable disease-free, overalland post-recurrence survival curves to those of receptor-negativebreast cancer patients. In the patient subgroups: premenopausal,stage III, more than four positive lymph node metastases, postoperativeadjuvant tamoxifen therapy, a significantly favorable prognosiswas recognized in either estrogen or progesterone receptor-positivepatients. Both receptors are thought to be useful prognosticindicators for patients with advanced tumors or for those receivingpostoperative adjuvant tamoxifen therapy. When the cut-off valuewas changed, the maximum significant difference in prognosisbetween receptor-positive and receptor-negative patients wasobserved at 5 fmol cytosol protein/mg for the estrogen receptoror 10 fmol/mg cytosol protein for the progesterone receptor.A more detailed examination should be made on the cut-off valuesof both receptors.     

CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.