Neoadjuvant chemotherapy promotes the expression of HER3 in patients with ovarian cancer
Takaaki MizunoYuki KojimaKan YonemoriHiroshi YoshidaYukiko SugiuraYohei OhtakeHitomi Sumiyoshi OkumaTadaaki NishikawaMaki TaniokaKazuki SudoAkihiko ShimomuraEmi NoguchiTomoyasu KatoTatsunori ShimoiMasaya UnoMitsuya IshikawaYasuhiro FujiwaraYuichiro OheKenji Tamura
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Abstract:
HER3 (erbB3) signaling serves an important role in the development and chemoresistance of ovarian cancer, and is activated by chemotherapy. To evaluate the influence of neoadjuvant chemotherapy and other clinical factors on the expression of HER3, as well as to examine its role as a prognostic marker, the present study evaluated archived tissues from patients who underwent surgery for ovarian cancer between 2011 and 2018 at our hospital. Immunohistochemical staining for HER3 was performed using formalin-fixed paraffin-embedded surgical specimens and biopsy samples. In total, data from 111 patients with sufficient surgically resected tumor samples were extracted. A total of 28 patients with histology type high-grade serous carcinoma (HGSC) had specimens available from both pre-chemotherapy biopsies and post-chemotherapy surgery. High HER3 expression (HER3-high) was observed in 64 patients (58%), whereas low HER3 expression (HER3-low) was observed in 47 patients (42%). Multivariate logistic regression analysis identified neoadjuvant chemotherapy [odds ratio (OR), 7.49; 95% confidence interval (CI), 2.48-22.64; P<0.001) and non-HGSC histology (OR, 5.42; 95% CI, 1.99-14.78; P<0.001) as significant predictive factors for HER3-high. In pre-chemotherapy biopsy specimens, 15 patients were HER3-high and 13 were HER3-low. After chemotherapy, eight of 13 patients with HER3-low exhibited a change in status to HER3-high, with a trend toward poorer progression-free survival compared to that of patients whose status remained HER3-low. In conclusion, HER3 overexpression was revealed to be common among patients with ovarian cancer, especially in those with non-HGSC histology. In addition, HER3 expression may be promoted by chemotherapy. These findings suggested that patients with ovarian cancer are good candidates for emerging HER3-targeting therapies.Keywords:
Histology
Background/Aim: Immunohistochemistry (IHC) enables visualisation of the distribution of specific proteins, the differentiation of benign and malignant tumours, and the site and origin of a primary tumour. Surgical pathologists commonly examine tumours with extensive necrosis or non-viable tissue that may affect an accurate diagnosis. Materials and Methods: We investigated the sensitivity and specificity of IHC on necrotic samples derived from adenocarcinoma, squamous cell carcinoma (SCC) and melanoma using different markers. Results: Analysis of necrosis within tumours revealed 88% sensitivity and 56% specificity for melanoma, 95% and 92% for CK5/6, 95% and 83% for CK20, 37% and 95% for p63, 69% and 97% for Melan A, 88% and 92% for SOX-10, 98% and 56% for CKAE/AE3 and 75% specificity for CK7. Conclusion: Antibodies should be considered reliable markers for demonstrating the epithelial nature of a suspected tumour. Immunohistochemistry of necrotic tissues may provide clinically useful information.
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Recurrent ovarian cancer is a lethal disease, and few patients can be cured. Although most patients receive standardized surgery and chemotherapy, the status of recurrent disease is heterogeneous. The site of recurrence and the survival intervals after recurrence are also widely distributed. Among a number of factors, many clinical trials identified time to recurrence was the factor most related to chemosensitivity at first relapse. The current recommendation for platinum sensitive ovarian cancer is a carboplatin containing combination chemotherapy. Generally, a single agent is chosen for platinum resistant ovarian cancer. Patients with single site recurrence and a long disease free interval are candidates for secondary cytoreduction, which may provide longer survival. There are several treatment choices at first relapse, and disease status, chemotherapy-free interval, and the patient's condition play a major role in the decision making process.
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Abstract: Epithelial ovarian cancer is the most lethal gynaecological malignancy with an estimated 295,414 new cases and 184,799 deaths around the world. Cytoreductive surgery and combination chemotherapy have remained a standard therapy for decades. The majority of women diagnosed with ovarian cancer will receive systemic chemotherapy for recurrent or advanced diseased. In recent years, therapies such as anti-angiogenics, PARP inhibitors, and dose-dense chemotherapy have emerged as novel strategies against ovarian cancer. Dose-dense chemotherapy, usually with a carboplatin and paclitaxel regimen, has been proposed as an alternative to conventional chemotherapy for these patients. However, the results for different trails are inconsistent and dose-dense chemotherapy remains controversial. Results from the JGOG 3016 study showed a progression free survival and overall survival benefit, with increased neurotoxicity and anaemia. While the GOG 262, MITO-7, GOG 252 and ICON8 studies found no benefit on progression free survival, with a recent meta-analysis concluding that three weekly chemotherapy remains the standard of care. Ovarian cancer molecular subtypes and differences in pharmacogenetics between populations may explain the differences in response to dose dense chemotherapy, however our understanding of this factors is still lacking. Here, we reviewed the evidence for and against dose-dense chemotherapy and the possible factors for the different results among trials.
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Abstract Context.—Immunohistochemical staining for β-catenin may be used as an indicator of the integrity of the Wnt signaling and β-catenin degradation pathways. Among mesenchymal tumors, aberrant nuclear localization of β-catenin is seen in desmoid-type fibromatoses but has not been described for solitary fibrous tumors that may mimic the former lesions, especially in small biopsy samples. Objective.—To study the immunohistochemical expression of β-catenin in solitary fibrous tumors. Design.—We performed immunohistochemical staining for β-catenin in 12 solitary fibrous tumors, one of which showed histologic features of malignancy. Results.—All the tumors showed strong and diffuse reactivity for β-catenin. Four tumors (33%) showed nuclear staining for β-catenin, whereas the remaining tumors showed either a membranous or mixed membranous and cytoplasmic pattern of staining. The only histologically malignant tumor of the group showed a mixed membranous and cytoplasmic pattern of staining for β-catenin. Conclusions.—Immunohistochemical staining for β-catenin in solitary fibrous tumors does not show a consistent pattern, which may be due to differences in tumorigenesis. Larger studies with clinical follow-up are required for estimating the impact of the variable staining pattern on clinical behavior of these tumors.
Immunostaining
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To assess the value of disease stabilization (SD) as a predictor of survival following chemotherapy, data were analyzed from multicenter clinical trials in small cell lung cancer (SCLC) and ovarian cancer (OC) patients receiving various second-line chemotherapy regimens. In both patient populations, SD (lasting >8 weeks) and partial responses (PR) were associated with a survival benefit versus progressive disease (PD); interestingly, the survival benefit was similar between the two groups (PR and SD). These results suggest that, at least in these populations, SD may represent a potential benefit of chemotherapy and therefore the distinction between SD and PR may not be useful.
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This report presents the gross morphology, cytological, histological, ultrastructural and immunohistochemical features of two angiomyelolipomas of the liver. Diagnosis and classification of these tumors is difficult. There is no immunohistochemical and ultrastructural confirmation for Ito-cell pathogenesis of hepatic angiomyelolipomas.
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Background: BRCA1 immunohistochemistry (IHC) provides a rapid initial screen to detect BRCA1 dysfunction in ovarian cancer that resulting from genetic alterations. Aim: To assess the expression of BRCA1 protein by IHC analysis among a group of Iraqi ovarian cancer patients to evaluate the patterns of expression and its correlation with the clinicopathological parameters in attempting to evaluate a significance role of BRCA1 gene implication in ovarian cancer. Methods: Forty three paraffin embedded samples of ovarian cancer cases were analyzed for BRCA1dysfunction by IHC analysis. The semi-quantitative approach using modified histochemical score (H-score) was achieved to assess the patterns of BRCA1 gene expression. Results: Complete loss of BRCA1 nuclear expression was detected in 30.2% of the cases while, reduced expression occurred in 46.5% of cases, giving rise to 76.7% of all cases detected with altered BRCA1 nuclear expression. Altered BRCA1 expression was found to be higher in age group ≤ 45 years (78.3%) in comparison with those of ages >45 years. Altered BRCA1 expression was significantly correlated with the high grade and with the unilateral tumor site when compared with the low grade and bilateral tumor site (P≤0.05), and was insignificantly correlated with the high stage ovarian tumors, 11.6% of cases were detected by cytoplasmic BRCA1 expression and no association was found between cytoplasmic expression and tumor grade, stage and tumor site. Conclusion: Altered BRCA1 expression may play a significant role in the progression of ovarian cancer. Recommendation: BRCA1 IHC is a clinically useful approach to detect the BRCA1 dysfunction and the H-score assessment reflects good estimation for BRCA1expression patterns.
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Immunohistochemical staining for INI1 (BAF47) expression has been recently described. Loss of expression of INI1 as detected by immunohistochemical staining correlates with deletion and mutations of the INI1 gene in patients with malignant rhabdoid tumors and central nervous system atypical teratoid/rhabdoid tumors and as such is a sensitive and specific marker for these tumors. Loss of INI1 expression may rarely be encountered in other tumor types. This article reviews the utility of immunohistochemical staining for INI1 expression.
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Objective To analyze and evaluate the application of immunohistochemistry and electron microscopy in difficultly-diagnosed tumors in nervous system.Methods Four cases of nervous system tumors were studied with immunohistochemistry and electron microscopy. Antibodies used in immunohistochemistry included those essentially and frequently used antibodies in diagnosis of nervous system tumors.Results Based on microscopic observation of the Hematoxylin-Eosin staining slides and immunohistochemistry and electron microscopy results, we diagnosed the 4 cases as: supratentorial primitive neuroectodermal tumor (PNET), desmoplastic infantile astrocytoma(DIA), chordoid meningioma and neurofibroma, in accordance with WHO nervous system tumor classification in 2000. Conclusion Application of immunohistochemistry and electronmicroscopy in the diagnosis of difficultly- diagnosed tumors in nervous system is very important.
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