BackgroundActivins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG) bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases.MethodsParaffin embedded specimens of normal breast (NB - n = 8); florid hyperplasia without atypia (FH - n = 17); fibroadenoma (FIB - n = 17); ductal carcinoma in situ (DCIS - n = 10) and infiltrating ductal carcinoma (IDC - n = 15) were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively.ResultsFollistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed.ConclusionThe present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the present findings indicate that an increased FST and FLRG expression in breast proliferative diseases might counteract the anti-proliferative effects of activin in human breast cancer.
Follistatin is a potent native activin antagonist that is expressed in the normal mammary gland and in different breast proliferative diseases. Despite experimental evidence that follistatin can modulate the breast cancer cell cycle, the clinical significance of follistatin expression in these tumors is unknown. The aim of this study was to correlate the intensity of follistatin expression in invasive breast cancer with some of its clinical and pathologic features, such as the disease stage and the hormonal receptor status. Paraffin blocks of tumor samples that had been fixed in buffered formalin were obtained from 154 women subjected to surgery for breast cancer between 2008 and 2012. Sections from all paraffin blocks were cut and processed together by immunohistochemistry using a commercial monoclonal antibody to human follistatin. The intensity of follistatin staining was unrelated to the menopausal status, the disease stage, the grade, progesterone receptor expression, and local or systemic recurrence. However, follistatin immunoreactivity was significantly stronger in estrogen receptor (ER)-negative tumors than in ER-positive tumors. These findings suggest that follistatin expression in invasive breast cancer is unrelated to the disease severity and the risk of recurrence, but is more intense in ER-negative tumors.
Follistatin-like 3 (FSTL3) binds and inactivates activin, a growth factor involved with cell growth and differentiation. We have previously shown FSTL3 overexpression in invasive breast cancers, but its clinical relevance remained unexplored. Here we evaluate FSTL3 as a prognostic tool and its relation with clinical and pathological features of breast cancer. A cohort of 154 women diagnosed with invasive breast cancer between 2008 and 2012 was followed up for 5 years. Tumor samples were processed by immunohistochemistry to detect FSTL3 expression in tumor epithelium. FSTL3 expression was classified semiquantitatively and tested for possible correlation with age, menopause status, stage, tumor histological type and grade, estrogen receptor, progesterone receptor, and HER2 expression. Survival plots with Kaplan-Mayer statistics were used to assess whether FSTL3 expression predicted disease-free survival. Our findings show that FSTL3 staining was unrelated to menopausal status, histological type, disease stage, or receptor profile. However, the intensity of FSTL3 immunostaining correlated inversely with tumor size (r = -0.366, p<0.001) and with nuclear grade (p<0.01). The intensity of FSTL3 expression in the tumoral epithelium was not predictive of the disease-free survival (p = 0.991, log-rank test), even though the follow-up length and the study size were sufficient to detect a significant reduction in disease-free survival among women with stage III-IV compared to stage I-II disease (p<0.001). FSTL3 expression in invasive breast cancer is inversely associated with tumor size and nuclear grade but it does not predict disease relapse in the short term.
Introduction: Gynecomastia (GM) is a benign proliferation of glandular breast tissue in men. Some cases need surgical intervention. Traditional open surgery by semicircular inferior periareolar incision is the most common surgical approach. In order to obtain better esthetic results, some alternatives to open surgery have been proposed, such as liposuction, endoscopic mastectomy, and vacuum-assisted excision (VAE). Objective: To describe the technical surgical approach of ultrasound-guided VAE of GM and its results from a case series. Method: This is an evaluation of seven GM cases submitted to ultrasound-guided VAE with a 10G needle using the ENCOR® BD whole circumference automated breast biopsy system in Redimasto – Redimama, a Brazilian breast center. The result was considered good or satisfactory when it showed minimal remaining gland, good symmetry, no retraction, necrosis, hypertrophic scar, or displacement of the nipple-areola complex. All patients answered a questionnaire to evaluate their satisfaction and perception of the procedure. Results: Seven (7) patients with Simon grade 1 and 2 bilateral GM underwent ultrasound-guided VAE. No case of displacement, necrosis, or retraction of the nipple-areola complex, post-procedure bleeding, infection, skin necrosis, or asymmetry was detected. No patient reported decrease or change in nipple sensation or erection. All patients had bruises and hematomas that spontaneously resolved within 30 days. All results were considered good or excellent by patients and surgeons. Conclusion: Minimally invasive ultrasound-guided VAE is an excellent alternative for the treatment of GM. It is better indicated for Simon grade 1 and 2 GM, with good and excellent esthetic results, small scar, and low rates of nipple and areolar complications. It allows an outpatient procedure with low morbidity (local anesthesia) and fast recovery.
Objective: Pathological complete response rate (pCR), ypT0/is ypN0, after neoadjuvant chemotherapy (NAC) varies in each molecular subtype of breast cancer, being lower in hormone receptor-positive (HR+) tumors. The objective of this study is to analyze the pathological response rate (PR) only in the breast, only in the axilla or the pCR, correlating with the molecular subtypes. Methods: This is a retrospective observational study of stage II and III patients undergoing NAC between 2013 and 2020 at the Oncology and Mastology Service of Santa Casa de Misericórdia de Belo Horizonte – MG (SCMBH). This study was approved by the Research Ethics Committee of SCMBH with the number 3,787,212 complying with Resolution 196/96 of the National Council for Ethics in Research. Results: In all, 209 patients were selected with a mean age of 50.6 years; 22.0% were T2, 35.9% were T3, and 42.1% were T4; 17.2% were pre-NAC cN0 and 82.7% were cN+. Patients were divided into group A, RH+, with 147 patients (70.3%), and group B, HER2+ and TN, with 62 patients (29.7%). When comparing PR only in the breast, RH+ patients had a better result (4.8% versus 1.6%); as well as PR only in the axilla, 37.4% against 29.0%. When subdividing group A into RH+/HER2− and RH+/HER2+, the former presented better results in the breast (4.3% X 0%) and in the axilla (60.9% X 55.6%). Conclusion: Achieving pCR is not the only goal of NAC. Other benefits include the possibility of breast and axilla-conserving surgery. The study demonstrated good PR results in both the breast and the axilla in group A and in the RH+/HER2− subgroup. These responses allow for a less morbid surgical treatment, both aesthetically and because of the risk of lymphedema. The data presented provide a compelling rationale for the use of NAC in a molecular subtype considered to be relatively resistant to chemotherapy.
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