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.     

己糖激酶-Ⅱ在胃癌组织中的表达及其临床意义

目的探讨己糖激酶-Ⅱ(HK-Ⅱ)在人体胃癌组织中的表达情况及其临床意义,分析HK-Ⅱ与临床病理特征之间的关系。方法选取2013年3—9月在东南大学医学院附属江阴医院确诊的胃癌病患100例,切除标本,运用免疫组化及RTPCR方法检测胃癌组织及正常胃黏膜组织中HK-Ⅱ的表达情况,并分析其与性别、年龄、浸润深度、TNM分期、分化程度、淋巴结转移、脉管侵犯、肿瘤大小等的关系。结果 HK-Ⅱ在胃癌组织中的阳性表达率为68.00%,显著高于正常胃黏膜组织(P0.05)。HK-Ⅱ表达与性别、年龄、浸润深度无关(P0.05);与TNM分期、分化程度、淋巴结转移、脉管侵犯、肿瘤大小有关(P0.05)。胃癌组织HK-ⅡmRNA阳性率显著高于正常胃黏膜组织(P0.01)。结论 HK-Ⅱ在胃癌组织中高表达,可作为胃癌的恶性预后指标和临床治疗靶点。     

Possibility of D2-40 as a diagnostic and tumor differentiation-suggestive marker for some of phosphaturic mesenchymal tumors

Phosphaturic mesenchymal tumor (PMT) has been established as a tumor that causes tumor-induced osteomalacia (TIO) associated with mesenchymal neoplasm. Its lineage of differentiation has not been elucidated. Previously, the presence of lymphatic vessels inside PMTs has been documented using an anti-podoplanin antibody; the tumor cells of PMTs were reported to not react with it. In this study of 14 cases of PMTs, we used immunohistochemistry of D2-40, a relatively specific lymphatic endothelial marker, to see if they stained PMTs or not, with particular interest in its reaction with microcystic structures containing lymph-like fluid. We report that most of the PMTs (12 out of 14 cases; 86%) were immunostained by D2-40 in their tumor cells; D2-40-positive lymphatic vessels inside the tumor were also observed. We used a proportion score (0-4+), an intensity score (0-3+), and a total score (the sum of the proportion score and the intensity score) to quantitate our results. We report that 50% of cases (7 out of 14 cases) had a total score ≥ 4+; immunostaining of D2-40 in cases with a total score ≥ 4+ was easy to observe at a glance. Most of the tumor cells lining the microcystic structures were immunostained with D2-40. Thus, D2-40 could be a useful diagnostic marker of PMTs and it might also indicate that PMTs take a lymphatic endothelial immunophenotype.     

Stereological evaluation of fibronectin in the periurethral region of the transitional zone from normal human prostates compared with benign prostatic hyperplasia

The aim of this study was to assess the volumetric density (Vv) of the fibronectin in the periurethral region of patients with benign prostatic hyperplasia (BPH) and compare with a control group. Prostatic periurethral tissue samples were obtained from ten patients (age range 65 to 79 years, mean 66) with clinical symptoms of bladder outlet obstruction who had undergone open prostatectomy. The control group samples (periurethral tissue samples from the transitional zone) were collected from prostates obtained during autopsy of accidental death adults of less than 25 years. The volumetric density (Vv) of the fibronectin was determined with stereological methods from 25 random fields per sample using the point-count method with an M-42 grid test system. The quantitative data were analyzed using the Kolmogorov-Smirnov and Mann-Whitney U tests. The Vv in the control and BPH groups was 21.9% ± 1.5% and 29.1 % ± 1.2% in the fibronectin, respectively. BPH tissues presented a significant increase of fibronectin in prostatic periurethral region in the transitional zone that may cause lengthening of the prostatic urethra.     

Expression of immunohistochemical markers according to histological type in patients with early gastric cancer

Objective. We compared the biological characteristics of early gastric cancer (EGC) using immunohistochemical (IHC) staining among histological types. Materials and methods. IHC staining results were analyzed in 86 EGCs resected with endoscopic submucosal dissection to identify mucin phenotype and biological characteristics. Results. The histological type was classified as tubular adenocarcinoma (TAC), mixed adenocarcinoma (MAC), or poorly cohesive carcinoma (PCC). Significant differences in MUC-2 (34.4% vs. 10.7%, p < 0.05) and MUC-5AC (59.4% vs. 85.7%, p < 0.05) expression were observed between TAC and PCC. The poorly cohesive component of MAC showed stronger immunoreactivity to CD10 (46.2% vs. 14.3%, p < 0.05) but weaker reactivity to MUC-5AC (57.7% vs. 85.7%, p < 0.05), compared to that of PCC. E-cadherin and β-catenin expression levels significantly decreased in the poorly cohesive component of MAC (15.4% vs. 90.6%, p < 0.05; 7.7% vs. 90.6%, p < 0.05, respectively) and PCC (10.7% vs. 90.6%, p < 0.05; 14.3% vs. 90.6%, p < 0.05, respectively), compared to TAC. However, vascular endothelial growth factor expression significantly increased in the poorly cohesive component of MAC (42.3% vs. 9.4%, p < 0.05) and PCC (39.3% vs. 9.4%, p < 0.05), compared to TAC. Conclusion. IHC analysis showed that EGC histological types differ in terms of mucin phenotype and biological characteristics. The poorly cohesive components showed decreased E-cadherin and β-catenin expression levels and increased vascular endothelial growth factor expression. These characteristics may contribute to the poor prognosis of patients with MAC and PCC.     

Desmoplastic melanoma: an updated immunohistochemical analysis of 40 cases with a proposal for an additional panel of stains for diagnosis

Desmoplastic melanoma (DM) is histologically characterized by a proliferation of spindle melanocytes dispersed in a collagenous stroma that can be mistaken for a variety of neoplasms. The purpose of this study was to analyze 40 cases of DM with a comprehensive panel of immunohistochemical markers (KBA.62, p16, Ezrin, WT‐1, MITF‐1, SOX‐10, CD117, SOX‐2, nestin, PNL2, p75, MART‐1, gp100 and S100p) to obtain a more complete understanding of the potential use of these antibodies in the diagnosis of DM. We found that all cases of DM expressed p16, WT‐1, SOX‐10, nestin and S100p and 95% of cases expressed p75. There was variable expression with Ezrin, SOX‐2, KBA.62, MART‐1 and HMB‐45. Most DMs did not express MITF‐1, PNL2 and CD117. Conditions that may enter in the histologic differential diagnosis of DM, including dermal scars, fibromatosis and dermatofibromas were also studied. Nearly all control cases also stained positive for p16 but were negative for WT1, SOX10, nestin, p75 and S‐100p, as well as for most of the other markers tested. We conclude that a panel of S‐100p, WT1, SOX10, p75 and nestin may constitute the optimal panel with the most sensitive and specific combination of immunostain available for the diagnosis of DM.     

Paragangliomas Arising in the Head and Neck: A Morphologic Review and Genetic Update

Seventy percent of parasympathetic paragangliomas arise in the head and neck and are nonsecretory. Awareness of the differential diagnosis based on location, overlapping morphology, and immunohistochemical profiles aids in the correct diagnosis, particularly on limited tissue samples. Moreover, 30% to 40% of head and neck paragangliomas are known to be associated with hereditary syndromes, with the succinate dehydrogenase enzyme family comprising the most frequent association. The pathologist’s role is becoming increasing critical for facilitating optimal patient care beyond the initial tissue diagnosis of paraganglioma to include screening and documenting potential hereditary tumors requiring further patient counseling and testing.     

Ki67/SATB1 ratio is an independent prognostic factor of overall survival in patients with early hormone receptor-positive invasive ductal breast carcinoma

Biological diversity of breast cancer presents challenges for personalized therapy and necessitates multiparametric approaches to understand and manage the disease. Multiple protein biomarkers tested by immunohistochemistry (IHC), followed by digital image analysis and multivariate statistics of the data, have been shown to be effective in exploring latent profiles of tumor tissue immunophenotype. In this study, based on tissue microarrays of 107 patients with hormone receptor (HR) positive invasive ductal breast carcinoma, we investigated the prognostic value of the integrated immunophenotype to predict overall survival (OS) of the patients. A set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16) was used. The main factor of the variance was characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α; it was associated with histological grade but did not predict OS. The second factor was driven by SATB1 expression along with moderate positive HIF-1α and weak negative Ki67 loadings. Importantly, this factor did not correlate with any clinicopathologic parameters, but was an independent predictor of better OS. Ki67 and SATB1 did not reach statistical significance as single predictors; however, high Ki67/SATB1 ratio was an independent predictor of worse OS. In addition, our data indicate potential double prognostic meaning of HIF-1α expression in breast cancer and necessitate focused studies, taking into account the immunophenotype interactions and tissue heterogeneity aspects.