Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

干扰素-α诱导蛋白27在胰腺癌组织中的表达及临床意义北大核心

目的:探讨干扰素-α诱导蛋白27(IFI27)在胰腺癌组织中的表达情况及其临床意义。方法:免疫组织化学法检测IFI27蛋白在胰腺癌、癌旁及慢性胰腺炎组织中的表达情况,分析阳性表达与胰腺癌患者相关临床病理参数和预后的关系。利用生物信息学方法基于TCGA数据库分析IFI27在胰腺癌组织中的表达差异和预后相关性。结果:IFI27在胰腺癌组织中表达的阳性率高于癌旁以及慢性胰腺炎组织(P<0.05),且与血管侵犯、淋巴结转移以及肿瘤分化程度相关。胰腺癌患者的总体生存期与肿瘤分化程度、血管侵犯、淋巴结转移以及IFI27阳性表达相关。多因素分析显示IFI27阳性表达是胰腺癌患者预后的独立危险因素。基于TCGA数据库分析得出IFI27在胰腺癌组织中的表达量高于正常组织(P<0.05),生存曲线提示IFI27低表达患者的预后优于高表达患者(P<0.05)。结论:IFI27高表达的胰腺癌患者预后差,IFI27阳性表达是胰腺癌患者的独立预后指标。     

Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

Objective: Human epidermal growth factor receptor 2 (erbb2/HER2) overexpression, has now been implicatedin advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-EastIndia and to assess the impact of various demographic and clinical parameters on HER2 positivity. Methods: A total of68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examinationfrom September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational(epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved,standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters.Results: The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantlyhigher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patientswith well differentiated histology and was more common in patients with stage II and III diseases, but neither of theassociations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours(56% versus 44%, P=0.002). Conclusion: HER2 overexpression was evident in 56% of the North-East Indian patientswith locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlatedsignificantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expressionis recommended to provide a therapeutic advantage in Indian patients.     

Expression of DNA Damage Response Markers in Early-Onset or Familial Gastric Cancers

Background: Early-onset or familial gastric cancer (GC) is known to have clinicopathologic profiles different fromthose of sporadic GC. We aimed to compare DNA damage response marker expression between early-onset or familialGC and sporadic GC. Methods: GC samples were obtained from patients who underwent gastrectomy for GC at SeoulNational University Hospital. Immunohistochemical analyses of various DNA damage response markers, includingBRCA1, BRCA2, MRE11, RAD51C, and γH2AX, were performed using 54 early-onset GC, 59 familial GC, and 337sporadic GC tissue microarray samples. Correlations between marker expression and clinicopathologic features wereevaluated by univariate and multivariate analyses, and overall survival was analyzed. Results: The rate of γH2AXpositivity was significantly higher (p < 0.001) in early-onset or familial GC than in sporadic GC. In contrast, the rates ofMRE11 negativity and RAD51C negativity were significantly higher in sporadic GC than in early-onset or familial GC.BRCA1 negativity was associated with decreased overall survival in sporadic GC (p = 0.002), and MRE11 negativitywas associated with decreased overall survival in sporadic GC (p = 0.012). Conclusion: Our results show significantdifferences in DNA damage response marker expression between early-onset or familial GC and sporadic GC.     

Acsl4在浸润性乳腺癌组织中的表达及其临床意义

目的:探讨Acsl4在浸润性乳腺癌组织中的表达及其临床意义。方法:采用免疫组织化学法检测108例浸润性乳腺癌组织中Acsl4的表达。结果:108例浸润性乳腺癌组织中,33例(30.6%)阳性表达,75例(69.4%)阴性表达。组织学G3级的乳腺癌组织中Acsl4阳性率为42.3%(22/52),高于G1+G2级的阳性率(19.6%,11/56),差异具有统计学意义(P<0.05)。ER阳性组织的Acsl4的阳性率15.8%(6/38),低于ER阴性的病例(38.6%,27/70),差异具有统计学意义(P<0.05)。Acsl4的表达与患者年龄、肿瘤大小、淋巴结是否转移、HER2、PR、p53、Ki67的表达情况无统计学意义的相关性(P均>0.05)。结论:Acsl4在浸润性乳腺癌组织中存在异常表达,其阳性表达与乳腺癌患者组织学分级较高及ER阴性表达密切相关。     

Risk Categorization with Different Grades of Cervical Pre-Neoplastic Lesions - High Risk HPV Associations and Expression of p53 and RARβ

Objective: To identify high risk HPV associations by evaluating linked p16 overexpression and also the expressionof p53 and RARβ together with histopathology for risk categorization of cervical pre-neoplastic lesions. Materials andMethods: Immunohistochemical staining was performed on 100 cases of cervical pre- neoplastic lesions for expressionof biomarkers like p16, p53 and RARβ for comparison with haematoxylin/eosin (HE) findings. All the experimentallygenerated data were statistically analyzed. Results: In this study 70% cases showed overexpression of p16INK4Aincreasing progressively from CIN I to CIN II but reduced in CIN III (p <0.01). p53 oncoprotein expression was seenin 51% cases, again with increments from CIN I to CIN II with slight reduction in CIN III (p<0.01). Some 24% casesshowed negative immunoreactivity for the putative tumor suppressor gene RARβ (p>0.05). Conclusion: Our studyprovides support for the idea that p16 can be used to identify associations with HPV , as well as having potentialalong with p53 and RARβ for categorizing cervical pre-neoplastic cases having a higher risk of neoplastic conversion.Thus it may be concluded that accurate risk categorization can be achieved with the help of genetic markers as wellas histopathology.     

鲍温病中XB130的表达和意义及临床病理分析

目的:研究XB130在鲍温病皮损组织中的表达，探讨其在鲍温病发生发展过程中的作用，并探讨鲍温病的临床病理特点。方法:回顾性分析我院161例鲍温病的临床及病理资料并应用免疫组化法检测37例鲍温病组织及35例正常皮肤组织中XB130的表达情况。结果:鲍温病多发于老年人，无性别差异，但男性的平均确诊年龄低于女性，所有患者中躯干为最常见发病部位。XB130在鲍温病组织中表达降低， XB130在正常皮肤组织及在鲍温病中的阳性表达率及表达强度差异均有统计学意义（P＜0.05）。结论:鲍温病多发于老年人，无性别差异，男性患者发病普遍早于女性患者，所有患者中躯干为最常见的发病部位，女性患者头颈部发病最多见，男性则多发于躯干。XB130在鲍温病皮损中的表达明显低于正常皮肤组织，XB130可能参与鲍温病的发生与发展。     

RIPK3在皮肤基底细胞癌中的表达及意义

目的:研究RIPK3在皮肤基底细胞癌中的表达及意义。方法:应用免疫组化SP法检测皮肤基底细胞癌和正常皮肤组织中RIPK3蛋白的表达情况。用RIPK3特异性siRNA干扰RIPK3在原代表皮角质形成细胞HEKa中的表达，用Annexin V-FITC/PI双染法检测细胞凋亡的变化。结果:在所收集的正常皮肤组织中，RIPK3的阳性表达率为90.0%，而在皮肤基底细胞癌皮损中其表达呈明显下降，阳性率为7.5%，两组RIPK3蛋白的阳性表达率及表达强度的差异均具有统计学意义（P<0.001）。HEKa细胞特异性敲低RIPK3表达后细胞凋亡数量减少。结论:RIPK3在皮肤基底细胞癌中的表达显著低于正常皮肤组织，RIPK3在皮肤基底细胞癌中的异常表达可能是通过抑制细胞程序性死亡而在其发生发展过程中起作用。