Estrogen Receptor Immunohistochemistry Research Articles

Hormonal Receptor Expression in Endometrial Carcinoma: A Retrospective Immunohistochemical Study in a Nigerian Tertiary Hospital.

Background:Endometrial carcinoma is the commonest genital tract malignancy in most developed nations, but it lags behind cervical carcinoma and ovarian cancers in most developing nations including Nigeria. Estrogen has been described as a promoter of endometrial carcinogenesis.Objectives:The aim of this study was to demonstrate the frequency of estrogen receptor (ER) and progesterone receptor (PR) expressions of endometrial carcinoma and to correlate it with tumour grade.Materials and Methods:Cases of endometrial carcinoma diagnosed in the Department of Pathology over a 10-year period were reviewed retrospectively. The paraffin-embedded blocks were retrieved, and immunohistochemistry for ER and PR was performed on them. Haematoxylin and eosin (H&E) slides were reviewed, and tumours were graded by three independent pathologists. Data were analysed using SPSS version 22. The level of significance was set at P ≤ 0.05.Results:There were 44 cases of endometrial carcinoma. ER and PR were positive in 29.5% and 18.2% of endometrial carcinoma, respectively. There was no significant association between ER (P = 0.361) and PR (P = 0.204) expressions and histological grade of the tumour. The most common histological grade was grade 3 with 70% of cases (36 cases), whereas 13 cases (26%) were grade 2 and only 2 cases (4%) were grade 1.Conclusion:The positive expressions of ER and PR in endometrial carcinoma suggest that steroid receptor studies may be of potential benefit in the management of some patients with endometrial carcinoma. Future studies employing larger sample size are therefore recommended.

Estrogen and progesterone receptor in meningiomas: An immunohistochemical analysis.

Meningiomas are common slow-growing primary intracranial neoplasms attached to the dura mater and are composed of neoplastic meningothelial cells. Increased incidence of meningiomas in women with an increased tumor growth during pregnancy and a possible association with breast cancer suggested that female sex hormones have been involved in the growth of meningiomas. Antihormonal-targeted therapy would be beneficial in such patients. The aim of this study is to correlate the expression of estrogen receptor (ER) and progesterone receptor (PR) in meningiomas with gender, location, histological subtypes, and grade. This is a 3½-year prospective and retrospective study of intracranial and intraspinal meningiomas. Clinical details of all the patients were noted from the computerized hospital information system. Immunohistochemistry for ER and PR was performed. Statistical analysis was performed using Chi-square test. During the study period, there were 80 Grade I, 18 Grade II, and 2 Grade III meningiomas categorized as per the World Health Organization 2007 classification. The female-to-male ratio was 1.9:1 and the mean age was 47.8 years. ER was expressed in 2% of meningiomas. PR was expressed in 67.5% of Grade I and 66.6% of Grade II and none of Grade III meningiomas. Brain-invasive meningiomas showed 54.5% PR immunopositivity and negative for ER. ER and PR were expressed in 2% and 66% of meningiomas, respectively. Statistically significant relationship was not found between the positivity of PR in females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas.

Study of ER, PR, HER2/neu, p53, and Ki67 expression in primary breast carcinomas and synchronous metastatic axillary lymph nodes.

Breast cancer (BCA) is the second most common cancer among women in India and accounts for 7% of global burden of BCA. The axillary lymph node status is an independent prognostic factor. The combined estrogen receptor (ER), progesterone receptor (PR), and HER2/neu biomarker expression is a predictor of BCA status for therapeutic guidance. Studies have demonstrated that these biomarkers are unstable throughout their tumor progression. Varying concordance and discordance rates in the biomarker expression between primary breast carcinoma (PBC) and metastatic axillary lymph node (MALN) status are reported. This study was conducted for studying and comparing the expression of immunohistochemistry (IHC) markers, i.e., ER, PR, HER2/neu, p53, and Ki67 between PBC and their corresponding MALN for prognostication and therapeutic purpose. Sixty cases of PBC with metastasis to axillary lymph nodes diagnosed between years 2008 and 2014 were included in the study. A technique of manual tissue array was employed for cases subjected to IHC. Analyses of the expression of IHC markers were attempted between the PBC and their corresponding synchronous MALN and classified as concordant or discordant. Results were subjected to statistical analysis. Substantial agreement was observed for biomarker ER, PR, HER2/neu, p53, and Ki67 expression between PBC and MALN with k-value 0.79, 0.75, 0.89, 0.7, and 0.6, respectively. There was high concordance for the IHC markers: ER, PR, HER2/neu, p53, and Ki67 expression in matched pairs of PBC and corresponding synchronous MALN. However, the discordance noted in small subgroups cannot be overlooked. Thus, there is a need to perform ER, PR, HER2/neu, p53, and Ki67 IHC studies routinely in both PBC and MALN to help design therapies that are tailored to target the specific tumor clones and render maximum benefit to patients.

Clinicopathological significance of immunohistochemical expression of Filamin A in breast cancer.

BACKGROUND:Filamin A is an actin-crosslinking protein expressed in many malignancies, although its prognostic and therapeutic role in breast cancer is not studied. There is enigma regarding its dual role in cancer, the tumor-progressing or tumor-suppressing effects depending on the site to which it localizes in the cell. The current study aimed to detect Filamin A expression in breast cancer and its association with other biomarkers and other clinicopathological parameters and established risk factors in breast cancer so that it can be a potential site for targeted therapy.MATERIALS AND METHODS:One hundred female patients of histologically proven breast cancer who presented to our hospital over a 2-year period were included in the study. None of the patients received prior radiotherapy, chemotherapy, or immunotherapy. Patients with recurrent breast cancer are not included in the study. All study cases are subjected to immunohistochemistry for estrogen receptor, progesterone receptor, Her2 neu, and ki-67 from core biopsy tissue of cases diagnosed as breast carcinoma. Tissue sections were subjected to immunohistochemistry with anti-Filamin A.RESULTS:Filamin A is expressed in 69% of cases of invasive breast cancer in our study. There was no statistically significant relationship of Filamin A immunoexpression with histological grade, age, parity, oral contraceptive use, smokeless tobacco use, TNM staging, clinical staging, clinical prognostic staging, and also ER, PR, Her2 neu, and ki-67 status (P > 0.05). Thus, it appears to be an independent biomarker in breast carcinoma. Filamin A was expressed only in the cytoplasm in all our study cases. Filamin A expression can be observed in adjacent normal breast tissue and benign fibroadenoma tissues also, but the pattern of expression is mainly membranous with cytoplasmic positivity. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer.CONCLUSION:No significant correlation could be found between Filamin A expression and clinicopathological parameters in our study. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. Filamin A immunoexpression should be further correlated with metastasis-free survival period of breast cancer patients

1154P - Expression of estrogen receptor and programmed cell death-ligand 1 can be complementary prognostic factors in HPV-positive oropharyngeal squamous cell carcinoma

BackgroundOropharyngeal squamous cell carcinoma (OPSC) continues to increase in incidence with human papillomavirus (HPV) infection. Despite the good overall prognosis, it needs to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure to guide de-intensification regimens. This study aimed to investigate the expression of estrogen receptor (ER) and programmed cell death-ligand 1 (PD-L1) proteins according to the status of HPV infection and their prognostic implication in OPSCC patients. MethodsConsecutive 80 patients diagnosed with OPSCC with surgical treatment from 2004 to 2017 were included. Immunohistochemistry for ER and PD-L1 was performed formalin-fixed, paraffin embedded tissues. HPV status assessed with p16 immunohistochemistry and HPV DNA testing. ResultsER and PD-L1 expression were observed in 37.5% (30/80) and 60% (48/80), respectively. Both ER and PD-L1 protein expression were higher in HPV-positive OPSCC than in HPV-negative subgroup (47.5% vs. 9.5% for ER, 66.1% vs. 42.9% for PD-L1). There was no significant association between ER and PD-L1 expression (correlation coefficient: 0.105, p>0.05). Using Kaplan-Meier curves, PD-L1 expression was associated with longer recurrence-free duration (p=0.013), whereas ER expression was associated with prolonged overall survival (p=0.043). In subgroup analysis, PD-L1 expression was found to be an independent excellent prognostic factor for recurrence-free duration in HPV-positive OPSCC (p=0.002, HR=0.085 [0.018-0.399]). ER expression also tended to be associated with longer overall survival in the HPV-positive OPSCC subgroup, but no statistical significance was observed. In HPV-negative subgroup, both ER and PD-L1 expression were not associated with any clinicopathologic factor nor survival. ConclusionsER and PD-L1 expression can be complementary prognostic factors in HPV-positive OPSCC. It may allow us to investigate the independent role of anti-hormone receptors and the tumor microenvironment in the treatment of OPSCC. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Surrogate Molecular Classification of Invasive Breast Carcinoma: A Comparison Between Core Needle Biopsy and Surgical Excision, With and Without Neoadjuvant Therapy.

Surrogate molecular classification identifies different subtypes of invasive breast carcinoma on the basis of their immunohistochemical markers. The purpose of the study is to verify whether the immunohistochemical markers and surrogate molecular subtypes can be correctly assessed on the core needle biopsy (CNB) when compared with the corresponding surgical excision (SE), with or without neoadjuvant treatment (NAT). Cases with invasive carcinomas identified on both CNB and SE were retrospectively selected. With immunohistochemistry for estrogen receptors (ER), progesterone receptors (PgR), Ki67, human epidermal growth factor receptor 2 (Her2), and molecular analysis for Her2, surrogate molecular classification was determined in 4 and 5 groups, according to the 2013 St Gallen consensus. A total of 1067 cases was considered and complete data for surrogate molecular classification were available for 988 cases (655 without NAT, 333 with NAT). Without NAT, concordance was strong for ER and Her2, moderate for PgR, and weak for Ki67; concordance for surrogate molecular classification was moderate. After NAT, lower concordance rates were recorded, with significant reduction of PgR (P<0.001) and Ki67 (P<0.001). Without NAT, the surrogate molecular subtypes of breast carcinoma can be reliably assessed on CNB; Ki67 and/or PgR may be repeated on SE when values are close to cutoffs to avoid tumor subtype misclassification. After NAT, it seems advisable to repeat at least Ki67 and PgR.

Potential Role for a Panel of Immunohistochemical Markers in the Management of Endometrial Carcinoma

BackgroundIn order to improve the efficacy of endometrial carcinoma (EC) treatment, identifying prognostic factors for high risk patients is a high research priority. This study aimed to assess the relationships among the expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and the different histopathological prognostic parameters in EC and to assess the value of these in the management of EC. MethodsWe examined 109 cases of EC. Immunohistochemistry for ER, PR, HER2, and Ki-67 were evaluated in relation to age, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and grade, depth of infiltration, cervical and ovarian involvement, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis. ResultsThe mean age of patients in this study was 59.8 ± 8.2 years. Low ER and PR expression scores and high Ki-67 expression showed highly significant associations with non-endometrioid histology (p = .007, p < .001, and p < .001, respectively) and poor differentiation (p = .007, p < .001, and p <. 001, respectively). Low PR score showed a significant association with advanced stage (p = .009). Low ER score was highly associated with LVSI (p = .006), and low PR scores were associated significantly with LN metastasis (p = .026). HER2 expression was significantly related to advanced stages (p = .04), increased depth of infiltration (p = .02), LVSI (p = .017), ovarian involvement (p = .038), and LN metastasis (p = .038). There was a close relationship between HER2 expression and uterine cervical involvement (p = .009). Higher Ki-67 values were associated with LN involvement (p = .012). ConclusionsThe over-expression of HER2 and Ki-67 and low expression of ER and PR indicate a more malignant EC behavior. An immunohistochemical panel for the identification of high risk tumors can contribute significantly to prognostic assessments.

Invasive cribriform carcinoma of the male breast

Male breast cancer is rare and it accounts for about 1 % of all breast cancers. Men of African and Jewish descent have higher risk of developing breast cancer. Invasive cribriform carcinoma of the breast, which has a good prognosis, is rarer particularly in male patients and only few cases have been reported in the literature. A young adult male presented with a painless, left breast mass of one-year duration at the surgical out-patient department of the Lagos University Teaching Hospital. On examination, a 24x16x6 cm mass, involving all four quadrants, attached to the overlying skin and underlying structure, was palpated in the left breast. It was non-tender and there was no differential warmth. Imaging studies revealed a Breast Imaging Reporting and Data System (BIRADS) IV lesion. On histopathology examination, an infiltrating carcinoma which was disposed in a cribriform pattern was seen. The neoplasm comprised of fairly monomorphic cells that exhibited increased nucleocytoplasmic ratio, moderate eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli. Immunohistochemistry for estrogen receptor, progesterone receptor and HER-2 revealed a luminal A tumour. A diagnosis of invasive cribriform carcinoma of the breast was made. We report the first known case of invasive cribriform carcinoma of the breast in a male patient from Nigeria.

Molecular subtyping of carcinoma of the female breast in a tertiary teaching hospital in Northern Nigeria

Background: Cancer of the breast is globally the most common female cancer including in Nigeria. Newer treatment modalities are based on tumor immunophenotyping, thus the need to characterize these tumors among women with the disease in Northern Nigeria. Aims: This study aims to classify carcinomas of the breast diagnosed in the pathology laboratory of a teaching hospital based on their expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2/neu (HER2/neu) overexpression. Methodology: The histology slides of 478 carcinomas of the breast as well as the ER, PR, and HER2 immunohistochemistry records of 118 stained cases were retrieved and reviewed. Results: Age range of cases was from 20 to 80 years (mean = 46.9 ± 13). The most common histomorphologic entity was invasive carcinoma (NST) which accounted for 73.2% of cases. These were followed in frequency by invasive lobular carcinoma accounting for 6.8% of cases and invasive papillary carcinoma representing 6.5% of cases. Overall, 169 cases (37.6%) were Grade III tumors while Grades II and I tumors accounted for 35.1% and 27.3% of cases, respectively. Triple-negative tumors were the most common molecular subtype and comprised 46.6% of all cases. Luminal B (LUMB) was the least common and accounted for 8% of all cases. HER2 overexpression and LUMA were seen in 17.9% and 28.8% of cases, respectively. Conclusion: Carcinoma of the breast in the population studied occurs at a younger age than among Caucasians. The tumors are characterized by preponderance of invasive carcinoma (NST), high histological grade, and triple-negative phenotype.

Differential effect of parity on rat mammary carcinogenesis after pre- or post-pubertal exposure to radiation

Radiation exposure during the peri-pubertal period is a proven risk factor for breast cancer, whereas parity is an established protective factor. The present study investigated whether parity imposes differential protective effects against radiation-induced rat mammary carcinoma depending on the age at exposure. Pre- and post-pubertal female rats, irradiated or left unirradiated, were mated and allowed to nurse until weaning or left unmated. Appearance of mammary tumors was monitored, and serum concentrations of estradiol and progesterone were measured following weaning. Carcinomas were evaluated by immunohistochemistry for estrogen receptor, progesterone receptor, and the cell proliferation marker Ki-67. Parity reduced the risk of carcinoma in unirradiated and pre-pubertally irradiated rats but not post-pubertally irradiated rats. Although radiation exposure increased serum progesterone level, parity after pre-pubertal exposure significantly decreased the elevated progesterone to a normal level, reflecting a protective effect. Moreover, parity significantly decreased the proportion of hormone receptor–positive carcinomas after pre-pubertal exposure. Parity was also related to the observed positive association between progesterone receptor and Ki-67 indices in cancer tissue, implying progesterone receptor–dependent cell proliferation. Thus, parity protects against radiation-induced rat mammary carcinogenesis depending on the age at exposure; the mechanisms may involve changes in hormone levels and cancer tissue.

Stability of oestrogen and progesterone receptor antigenicity in formalin-fixed paraffin-embedded breast cancer tissue over time.

Use of archived formalin-fixed paraffin-embedded (FFPE) tissue is a standard method for evaluation of proposed prognostic and predictive tumour markers. However, little is known of the preservation of biomarker expression in old FFPE tumour blocks. We investigate the quality of immunohistochemical (IHC) oestrogen (ER) and progesterone receptor (PR) evaluation in FFPE tissue over time (1978-2000) using a large breast cancer tissue microarray (N=573) with access to receptor analyses in cytosol (CYT) at diagnosis, coexpression of other biomarkers and follow-up data. We found a good correlation between ER analysed with CYT at diagnosis and ER analysed with IHC in archived FFPE tissue from the same tumour. ER evaluation did not seem to be affected by tissue storage time. Nor was there any time-dependent difference in ERIHC correlation with other biomarkers (HER2, Ki67) or survival. Discordant cases were more often classified as ER-positive with IHC than with CYT. For PR, however, we found an increased correlation between methods in more recent time periods. This may possibly be explained by more reliable PRIHC results in newer samples, although other explanations may also contribute. Our results indicate stable ER expression in FFPE tissue archived for up to 40years.

Diagnosis of thoracic endometriosis with immunohistochemistry

Pathological and immunohistochemical features of thoracic endometriosis are not well understood. In the present study, we retrospectively analyzed the clinical and pathological diagnostic characteristics of 55 female pneumothorax cases. This study was a retrospective observation of 55 women aged from 8 to 62 years old who underwent surgery for pneumothorax from November 2001 through January 2018. Immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), and CD10 was performed for all cases. As controls, we analyzed resected specimens of spontaneous pneumothorax in men who received surgery. Of 55 cases, endometrial stroma and glands by Hematoxylin-Eosin (HE) stain was found in only one case. Thirty-seven cases (67.3%) were ER- and PR-positive in stromal bland spindle cells of the lung. The remaining 18 cases (32.7%) were ER-, PR-, and CD10-negative. The ER- and PR-positive specimens could be further classified according to 2 staining patterns: 'scattered pattern' and 'aggregated pattern'. Thirty-three cases (60.0%) were scattered and four cases (7.3%) were aggregated pattern. Only the aggregated pattern specimens exhibited positive staining for CD10. As the scattered pattern was also found in men, we only diagnosed the aggregated pattern cases as endometriosis. A diagnosis of thoracic endometriosis is simple when both endometrial stroma and gland are present. In cases of endometriosis with stroma only, a further classification of "aggregated pattern", in which immunohistochemistry is ER-, PR- and CD10-positive might be necessary for diagnosis.

Smoking, Sex, and Non-Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424).

To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = -15.8, P = .003) and nuclear ER-β (β = -12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P < .001) and ER-β (β = 25.9, P < .001) but lower total PR (β = -42.1, P < .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways.

Magnesium valproate ameliorates type 1 diabetes and cardiomyopathy in diabetic rats through estrogen receptors

Estrogen is known to exhibit cardioprotective and antihyperlipidemic action. Valproic acid has been shown to upregulate estrogen receptors (ERs) in breast and prostate cancer tissues. No pharmacological evaluations for magnesium valproate (MgV) so far have been done for diabetic cadio-lipidemic complications. Based on the above context, current study was undertaken to evaluate the therapeutic effectiveness of MgV in cardiac complications associated with type-1 diabetes mellitus in rats wherein diabetes was induced by single tail vein injection of streptozotocin (STZ, 45mg/kg, IV) in female Sprague Dawley rats and treatment of MgV (210mg/kg, PO) was given for eight weeks to diabetic animals, after which, various biochemical and cardiac biomarkers, hypertrophic, hemodynamic and histological parameters along with immunohistochemistry of ERs in the left ventricle (LV) were estimated. MgV treatment significantly controlled hyperglycemia and dyslipidemia, reduced elevated cardiac biomarkers and C-reactive protein(CRP), significantly improved hemodynamic functions and increased the rate of pressure development and decay. MgV also significantly reduced left ventricular hypertrophy index and cardiac hypertrophy index, LV wall thickness, LV collagen, cardiomyocyte diameter and prevented the oxidative stress with significant increase in Na+-K+-ATPase activity in LV. Moreover, MgV reversed STZ-induced histological alterations and decreased glycogen content in LV and increased the ERβ expressions in LV as evidenced by immunohistochemistry. The result indicated that MgV prevented disease progression in the early stage of diabetic cardiomyopathy which seems to be mediated by upregulation of estrogen receptors in LV tissue.

Breast cancer subtype discrimination using standardized 4-IHC and digital image analysis.

Breast cancer is a heterogeneous disease. Surrogate classification of intrinsic subtypes of invasive carcinomas by combined immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 (4-IHC) has increased steadily since the 2011 St Gallen symposium, due to its rapid subtyping of tumors at a reasonable cost. An important step in improving 4-IHC reproducibility and reliability will be to provide reference values from the routine use of standardized 4-IHC followed by image analysis. The aims of the current study were (1) to analyze invasive breast carcinomas using standardized 4-IHC and quantitative image analysis and (2) to compare the results obtained in the classification of biological subtypes using current Ki67 and PR threshold values proposed by different authors to sub-classifying the luminal A-like and the luminal B-like (HER2-negative) subtypes. Five hundred twenty-one tumors were analyzed by standardized immunohistochemistry, with automatic image analysis, and HER2 FISH technique. Positivity for ER was found in 82.7% and for PR in 70.1% of cases. Using the Allred scoring system, hormone receptor results showed a bimodal distribution, particularly for ER. HER2 positivity was found in 15.7% of cases, and the mean Ki67 score was 32.3%. Using the most recently proposed surrogate definitions for the classification of luminal breast cancer subtypes, the percentages of different subtypes that we found were similar to those published with genomic platforms: 40.7% luminal A-like, 32.4% luminal B-like/HER2-negative, 9.8% luminal B-like/HER2-positive, 6.0% HER2-positive, and 11.1% triple negative. Standardized 4-IHC with automatic image analysis constitutes a low-cost method for surrogate definitions of biological subtypes of breast cancer that delivers accurate results in a day.

Comparison of Estrogen, Progesterone and Her2 Receptors in Primary Breast Cancer and Paired Metastatic Lymph Nodes: An Immunohistochemical Study

Background: Immunohistochemistry (IHC) of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2) are important prognostic factors of breast cancer. However, discordance between IHC findings of primary tumor and ipsilateral metastatic lymph nodes (IMLNs) has been reported that might affect the criteria for adjuvant therapies in breast cancer in the future. Methods: Sample size of the current study was estimated 50 (Macnemar test). We performed IHC for ER, PR, and Her2 on IMLNs of 50 paraffin embedded blocks of breast cancer patients with regional lymphadenopathy during the period. All-red score 2 was regarded as negative and 3 as positive for ER/PR. Her2 results were classified to 1+ ( 0 and 1+), 2+, and 3+. We used SPSS 16 to insert and analyze the data. Results: Mean age of patients was 49 yrs, and mean tumor size was 4.8 ± 3.53 cm. Twenty-four samples were pN1, 17 pN2, and 9 pN3. ER and PR were positive in 50% and 52 % of tumoral samples and 78% and 76% of IMLNs, respectively (fisher exact test, P = 0.003 and P = 0.011, respectively). The discrepancy between IHC of primary tumor and IMLNs for ER, PR and Her2 was 32% (P = 0.000), 24% (P = 0.002), and 48%, respectively. Overall, 34 patients (68%) showed disagreement in at least one of their receptors. Conclusions: Discrepancy between IHC results of primary tumor and IMLNs was significant. Since metastatic clones in metastatic lymph nodes (MLNs) are potential sources of systemic metastasis, routine IHC on MLNs could play an important role in determining prognosis, indication for FISH, and finally, choosing adjuvant treatment.

Distribution patterns of 21-gene recurrence score in 980 Chinese estrogen receptor-positive, HER2-negative early breast cancer patients.

AimThe current study aimed to explore the distribution patterns of 21-gene recurrence score (RS) assay in Chinese early breast cancer patients.MethodsNine hundred and eighty consecutive estrogen receptor(ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients treated at Ruijin Hospital, Shanghai Jiaotong University, School of Medicine from 2009 to 2016 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay of 21 genes were conducted in paraffin-embedded tumor tissue to calculate the RS. Co-relations of RS and clinico-pathologic factors were evaluated. Concordances of RT-PCR and immunohistochemistry (IHC) tests were measured. Logistic regression were applied to determine independent variables associated with RS.ResultsThe median RS of 980 patients was 23(0~90), and the proportions of patients categorized as having a low, intermediate, or high risk were 26.1%, 49.3% and 24.6%. The distribution of RS varied significantly according to different tumor grade, T stage, progesterone receptor(PR) status, Ki67 index and molecular subtypes (p<0.05). Grade, PR status and Ki67 index were identified as independent variables associated with RS. The concordance rates between RT-PCR and IHC test were 98.8% and 88.3% for ER and PR status, and there were weak to moderate correlation between IHC and RT-PCR tests for ER, PR expression and Ki67 index.ConclusionsRS correlated significantly with grade, T stage, PR status, Ki67 index and molecular subtypes in Chinese early breast cancer patients. Grade, PR status and Ki67 index could independently predict RS. ER, PR status and Ki67 index between RT-PCR and IHC test had remarkable concordance.

Sex steroid receptor expression in idiopathic pulmonary fibrosis

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF.

Correlation of Hormone Receptor and Human Epidermal Growth Factor Receptor-2/neu Expression in Breast Cancer with Various Clinicopathologic Factors.

Background:A significant development in the breast carcinoma management is the correlation between the presence of hormone receptors in the tumor and response to hormonal therapy and chemotherapy. Human epidermal growth factor receptor-2/neu (Her-2/neu) overexpression also serves as a very useful parameter to predict response to herceptin.Aim of Study:The study was conducted to correlate immunohistochemical expression of markers such as estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu with various clinicopathologic parameters.Materials and Methods:The study included 509 cases of breast carcinoma over a period of 5 years (from May 2009 to May 2014). Immunohistochemistry (IHC) for ER, PR, and her-2/neu was performed.Results:ER positivity was observed in 42.8% (218/509) cases, PR positivity in 31.8% (194/509) cases whereas her-2 neu positivity was seen in 40.7% (203/509) cases. Triple marker (ER, PR, and Her-2/neu) negative cases were 23.6% (120/509) cases. ER and PR expression was found to have a statistically significant correlation with tumor grade. Statistically significant correlation was observed between tumor size and tumor grade and her-2/neu expression. Her-2/neu expression showed statistically significant association with tumor stage. As the tumor grade increased, the proportion of triple-negative cases went on increasing, which was statistically significant.Conclusion:IHC has an increasingly important prognostic role in determination of factors that affect clinicopathologic features. Nevertheless, the results of this large series showed different patterns of findings with respect to clinicopathologic features.

Proposal of a Provisional Classification of Sebaceous Carcinoma Based on Hormone Receptor Expression and HER2 Status.

Despite recent progress in comprehensive genetic analysis, little is known about the molecular pathogenesis of sebaceous carcinoma. On the basis of the ontogenic proximity of sebaceous and mammary glands, we designed an intrinsic classification for sebaceous carcinoma adapted from that of breast cancer and evaluated its clinical significance. We investigated 42 cases of sebaceous carcinoma, including 32 ocular and 10 extraocular cases. Immunohistochemical analyses for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, Ki67, and CK5/6 and fluorescence in situ hybridization for the HER2 gene were performed. The immunohistochemistry for ER, PR, and AR showed positivity in 18 (42.9%), 11 (26.2%), and 34 (81.0%) cases, respectively. Expression of the HER2 protein was found in 10 (33.8%) cases, whereas extra copies were found in 3 (7.1%). According to our system, there were 16 (38.1%) cases of the luminal 1 subtype, 4 (9.5%) of the luminal 2 subtype, and 7 (16.7%) of the HER2 subtype, respectively. Fifteen cases (35.7%) belonged to the triple-negative group. In univariable analysis, loss of AR was significantly associated with shorter disease-free survival (P=0.020), whereas the expression of HER2 was associated with a better outcome with borderline significance (P=0.060). The luminal 2 subtype showed the best survival, and the all-negative subtype showed the worst (P=0.001). In multivariable analysis, negativity of PR or AR, low CK5/6, and female sex were independent poor prognostic factors (all P<0.05). This is the first study to categorize sebaceous carcinoma on the basis of the possible link between its molecular pathogenesis and future therapeutic applications.