Background Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens.
Methods This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary’s Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0–8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers.
Results In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively.
Conclusions CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.
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Background Adenocarcinoma (ADC) of the lung exhibits different clinicopathological characteristics in men and women. Recent studies have suggested that these differences originate from the expression of female sex hormone receptors in tumor cells. The aim of the present study was to evaluate the immunohistochemical expression of female sex hormone receptors in lung ADC and determine the expression patterns in patients with different clinicopathological characteristics.
Methods A total of 84 patients with lung ADC who underwent surgical resection and/or core biopsy were recruited for the present study. Immunohistochemical staining was performed for estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR), epidermal growth factor receptor (EGFR), EGFR E746- A750 del, and EGFR L858R using tissue microarray.
Results A total of 39 (46.4%) ERα-positive, 71 (84.5%) ERβ-positive, and 46 (54.8%) PR-positive lung ADCs were identified. In addition, there were 81 (96.4%) EGFR-positive, 14 (16.7%) EGFR E746-A750 del–positive, and 34 (40.5%) EGFR L858R–positive cases. The expression of female sex hormone receptors was not significantly different in clinicopathologically different subsets of lung ADC.
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Background Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype.
Methods The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics.
Results ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy.
Conclusions Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.
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Background Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients.
Methods To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival.
Results PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses.
Conclusions Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.
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Background The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process.
Methods Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples.
Results The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found.
Conclusions Our data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.
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Selective immuno-modulatory effect of prolactin upon pro-inflammatory response in human fetal membranes Pilar Flores-Espinosa, Eduardo Preciado-Martínez, Araceli Mejía-Salvador, Gabriela Sedano-González, Luisa Bermejo-Martínez, Adalberto Parra-Covarruvias, Guadalupe Estrada-Gutiérrez, Rodrigo Vega-Sánchez, Isabel Méndez, Braulio Quesada-Reyna, Andrea Olmos- Journal of Reproductive Immunology.2017; 123: 58. CrossRef
BACKGROUND Despite an increased incidence of endometrial carcinomas in young Korean women, clinicopathologic characteristics and treatment outcomes have not been analyzed. METHODS We investigated clinicopathologic characteristics of endometrial carcinoma in 48 women who were under the age of 40 in order to determine treatment guideline. RESULTS According To The Criteria Of The Korean Society For Obesity, 70.8% Of Study Patients Were Overweight Or Obese, With An Average Body Mass Index (Bmi) Of 26.0 kg/m2. Twelve Patients Received Progesterone Treatment Only, And 6 Of Them Later Had Successful Pregnancies. The Histologic Subtype Was Endometrioid Adenocarcinoma In All Patients. Figo Stages Were 1A(41.7%), 1B(47.1%), II (2.8%), IIB2.8%), IIIA(2.8%), And IIIC (2.8%). Figo Grades Were Grade 1 (79%) Or 2 (21%).
The Average Depth Of Invasion, Excluding Stage 1a, Was 4.6 Mm In The Hysterectomy Specimens. Two Patients Were Given Post-operative Radiation Treatment And 4 Were Treated With Chemotherapy. All But One Case Had An Uneventful Postoperative Course During Follow-up. CONCLUSIONS A majority of endometrial carcinomas in young Korean women were associated with an early FIGO stage, favorable histologic subtype and grades, and a good prognosis. Progesterone treatment with close observation was a successful treatment option in a selected group of young patients.
Estrogen and progesterone receptors exist in the epithelial and stromal cells of the endometrium. Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions of estrogen and progesterone in epithelial and stromal cells. This study was performed to evaluate the differences estrogen and progesterone receptor(ER/PR) expression in the epithelial and stromal cells of endometrial hyperplasias and adenocarcinomas using immunohistochemical methods. Immunohistochemical analysis of proliferating cell nuclear antigen(PCNA) was done to evaluate a possible correlation between PCNA and hormone receptor expression. Evaluation was based on samples from 31 simple hyperplasias, 30 complex hyperplasias, and 32 adenocarcinomas. The immunohistochemical expression of ER, PR and PCNA in epithelial and stromal cells were examined according to a scoring system based on the percentage of positive cells and the staining intensity. The results were as follows; 1) The expression of ER and PR in epithelial cells showed a graded, significant decreases in simple hyperplasia, complex hyperplasia and endometrial carcinoma, in that order(ER: P=0.008, PR: P= 0.026). 2) PR expression in the stromal cells showed a significant decrease between hyperplasia and adenocarcinoma(P=0.003). The difference in ER expression was not significant. 3) In stromal cells, the decrease in PR expression was more prominent than the decrease in ER expression when complex hyperplasia was compared to simple hyperplasia. 4) The PCNA expression in simple and complex hyperplasia and adenocarcinoma was not higher than the expression of PCNA in nomal proliferative endometrium. There was no significant difference in PCNA expression between simple and complex hyperplasia and adenocarcinoma(P=0.073). 5) A negative correlation between PCNA and ER/PR expression was not demonstrated in simple and complex hyperplasia, or in adenocarcinoma. Endometrial hyperplasia and adenocarcinoma are probably related to a paracrine action of estrogen and progesterone in epithelial and stromal cells. A progressive loss of PR expression in stromal cells may induce abnormal proliferation of endometrium due to a disrupted hormonal balance.
This study aimed at assessing the usefulness of paraffin wax sections for demonstration of ER(estrogen receptor) and PR(progesterone receptor), using brief microwave processing rather than proteolytic predigestion. The receptor status of a breast cancer is often into consideration when planning treatment nowadays. As biochemical receptor assays require large amount of fresh tumor tissue and are not always available for all tumors, pathologists are now increasingly asked to provide a service for the assessment of the receptor status in tissue routine sections. Until recently, immunohistochemical demonstration of receptors was used in frozen sections. Therefore, routinely processed paraffin wax sections of 25 cases of breast carcinoma with known ER and PR concentrations, estimated by the standard DCC(dextran-coated charcoal) biochemical assay, were examined using the ABC immunoperoxidase technique. The results were assessed semiquantitably, using a five grade scoring system. Of the 25 cases examined, with DCC cutoff point being <10 fmol,71% and 75% in positivity of each ER, PR receptor is concordant. Statistic analysis demonstrates high relationship between scoring system of IH method and DCC value in ER (R=0.6061, p=0.001) and PR (R=0.5832, p=0.001). The IH method can provide easily assessed reliable positive information about ER, PR status of breast carcinoma using routinely processed paraffin wax sections.
Estrogen receptor(ER) and progesterone receptor(PR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in leiomyomas and myometrium from same patients from 38 women in various stages of the menstrual cycle, menopause and pregnancy. Two postpartum uteri are also included. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution, and the results were compared with those of PCNA index. In all samples, ER and PR localized within the nuclei of target cells. The histochemical score of ER in leiomyoma was significantly greater than that found in myometrium. But ER in leiomyoma was expressed in cyclic fashion(r=0.45, P=0.006), like as in myometrium, throughout the menstrual cycle, paralleled by a concomitant, though delayed. In contrast, PR content constantly maintained in myometrium and leiomyoma throughout menstrual cycle, and there was no significant difference between them. However, leiomyoma and myometrium of pregnancy showed a significant reduction in the amount of ER and PR localized. PCNA index in leiomyoma(14.9+/-24.4) was also significantly higher than that found in myometrium(2.1+/-3.3). The index declined throughout the secretory phase. The leiomyoma had increased PCNA index during pregnancy, while the increasing rate in leiomyoma was lower than that of myometrium. The growth potential of leiomyomas is appearently higher than that of myometrium under the high progesterone level. The most of neoplasm with high PCNA index(10 above) contained absolute or relative abundant PR or ER content. Alteration of receptor content may be an important mechanism in steroid dependent growth of leiomyoma and may provide information useful in the clinical management of this neoplastic disorder.
Estrogen receptor(ER) is a soluble form of hormone receptor protein which is located in the nucleus and cytoplasm of a cell is found in 60% of cases of the cells of breast carcinoma. Fifty to sixty percent of ER positive breast carcinoma responds to antihormone therapy wheres the response rate is only 5% in ER negative tumors. Currently, the ER assay has become a standard index in the management and prediction of the prognosis of advanced breast carcinoma. Semiquantitative biochemical assay, dextran-coated charcol(DCC) assay, to measure ER from fresh tissue was first developed by Korenman in 1970 using isotope-labled ertradiol, has been widely utilized. In 1978, Kurzon newly developed immunocytochemical assay(ICA) employing monoclonal antibody against those hormone receptors to detect intracellular localization of ER and progesterone receptor (PR). The results of the assay have been reported by many investigators thereafter. The purpose of this study was to evaluate the hormonal receptors with a monoclonal antibody using an immunoperoxidase procedure to detect both estrogen and progesterone receptors (ER-immunocytochemical assay:ER-ICA and PR-immunocytochemical assay:PR-ICA) in 59 cases of paraffin embedded sections from formalin-fixed and routinely processed breast carcinoma tissue. Concomitantly, fine-needle aspiration biopsy cytology of the breast cancer from 29 women were assayed for ER/PR receptors. Results were compared with quantitative biochemical values determined from dextran-coated charcoal(DCC) assay on the fresh tumor tissue obtained subsequently from the surgery. ER-ICA showed positive result in 22 out of 36 DCC-positive cases(sensitivity, 61.1%) and negative in 23 out of 23 DCC-negative cases (specificity, 100.0%). PR-ICA was positive in 33 out of 35 DCC-positive cases(sensitivity, 94.3%) and negative in 16 out of 24 DCC-negative cases(specificity, 66.7%). The value of ER-ICA or PR-ICA positivity were roughly correlated with the concentration of ER/PR receptors analyzed by DCC method. The results of both methods were correlated with the nuclear grade of the tumor(ICA:p=0.002, DCC: p=0.015) but were not correlated with histologic grade(ICA: p=0.323, DCC: p=0.0164). ER-ICA positivity was correlated with lower incidence of axillary node metastasis (p=0.021) but no significant correlation between PR-ICA positivity and node metastasis(p=0.171). Both ER/PR-ICA positivity were not correlated with age(p=0.924) and tumor size(p=0.663). The score of ICA particularly ER was proportional to DCC level(ER: r=0.5, p=0.000, PR: r=0.2, p=0.000). ICA concordance with DCC of ER and PR were 76.3% and 83.1%, respectively. The concordance of PR-ICA and DCC was proportional but was statistically less significant. In aspiration biopsy cytology the concordance of ER/PR-ICA and DCC were 72.4% and 65.5%, respectively. Immunocytochemical staining to identify ER/PR receptors from the tissue of breast carcinoma would be tested as a mean to substitute for the conventional DCC method.
During evaluation of follow-up curettage of endometrial hyperplasia after progesterone treatment, we have noticed that the foci of squamous or morular metaplasia are persistent or even markedly increased after the hyperplastic glands have all disappeared. These observations have led us to study the histological changes of squamous or morular metaplasia in the hyperplastic endometrium after progesterone treatment and to examine the changes of estrogen receptors(ER) and progesterone receptors(PR) to find out, if there is any pathogenetic role of progesterone administration on the squamous or morular metaplasia.
Squamous or morular metaplasia was associated in 21 cases (13.5 %) out of 156 endometrial hyperplasia during the study periods and all of them were associated with complex hyperplasia, but not associated with simple hyperplasia. At follow-up curettage after progesterone treatment, squamous metaplasia newly appeared in 3 cases(20 %), markedly increased in 4 cases(26.7%), persisted in 4 cases(26.7%) and decreased in 4 cases(26.7%), even after hyperplastic glands have all disappeared or were markedly decreased. On immunohistochemical staining, metaplastic foci showed ER- and PR- in 13 cases (87 %) in contrast to the surrounding endometrium and the remaining 2 cases showed minimal ER+ and PR+ confined to several nuclei. Intensity or staining pattern of ER and PR in metaplastic foci were not changed with progesterone treatment. In the background endometrium, intensity of glandular ER+ and PR + was higher than that of the stroma at the initial curettage, however, progesterone treatment predominantly down-regulated glandular ER+ more than stromal ER+. Increment or persistence of squamous metaplasia along the progesterone treatment seemingly would implicate hormonal influences as playing a significant role in the formation of squamous or morular metaplasia and the absence of cellular receptors for these hormones in the metaplastic foci may suggest qualitative changes in the receptors.
We describe herein a case of meningioma showing three recurrences and in the end malignant transformation. To compare the differences of MIB1, p53 and progesterone receptor expressions in benign, recurrent and malignant meningiomas of the same patient, we performed immunohistochemical stainings for those markers. MIB1 and p53 reactivities were increased in proportion to histologic aggressiveness. By contrast, the progesterone receptor expression was noted in benign meningioma but not in malignant meningioma.
This study was carried out to evaluate the expressions of the p53 protein, the estrogen receptor (ER) and the progesterone receptor (PR), as well as the relationship between their expressions and clinicopathologic prognostic factors with storage duration of a paraffin block, and correlation between the p53 protein, the ER and the PR expressions in 29 cases of leiomyosarcoma of soft tissue.
The expressions of the p53 protein, the ER and the PR were semiquantiatively analyzed in paraffin sections by the immunohistochemical method out of 29 cases the p53 protein, ER and PR were expressed in 9 (31.0%), 2 (6.9%) and 5 (17.2%), respectively. The expression of the p53 protein was not significantly associated with sex, age, anatomic site, tumor size, tumor depth, histological differentiation or mitotic rate (p>0.05), but statistically correlated to storage duration of a paraffin block (p=0.028). There was no significant relationship between the expression of the ER and all the clinocopathological prognostic factors with storage duration of a paraffin block (p>0.05). The expression of the PR was related to the histological differentiation (p=0.02), but not related to other clinicopathological prognostic parameters and storage duration of a paraffin block (p>0.05). The expression of the p53 protein and the PR had a significant relationship (p=0.022), but the expression of the p53 protein and the ER had no significant correlation. In conclusion, these results suggest that the expression of the p53 protein and the PR may play a role in development and growth of soft tissue leiomyosarcoma. Further studies of large numbers are needed to clarify the exact relationship between tumorigenesis and the p53 and the PR expressions in leiomyosarcoma of soft tissue.