ABSTRACT
Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. Heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated, by immunohistochemistry, the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n = 60) treated with doxorubicin (DOX)- or epirubicin (EPI)-based monochemotherapy. Serial biopsies were taken at days 1, 3, 7, and 21, and compared with prechemotherapy and surgical biopsies. After surgery, the patients received additional chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil. High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P < 0.001), but the drug did not affect the cytoplasmic expression of the HSPs. Infiltrating lymphocytes showed high nuclear HSPA (P < 0.01) levels at postchemotherapy. No correlations were found between HSPs expression and the clinical and pathological response to neoadjuvant therapy. However, in postchemotherapy biopsies, high nuclear (>31 % of the cells) and cytoplasmic HSPA expressions (>11 % of the tumor cells) were associated with better DFS (P = 0.0348 and P = 0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy indicating the need to change the administered drugs after surgery for overcoming drug resistance.
Subject(s)
Anthracyclines/therapeutic use , Antibiotics, Antineoplastic/therapeutic use , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast/pathology , HSP70 Heat-Shock Proteins/analysis , Neoadjuvant Therapy , Adult , Aged , Breast/drug effects , Breast Neoplasms/pathology , Doxorubicin/therapeutic use , Epirubicin/therapeutic use , Female , Follow-Up Studies , HSP27 Heat-Shock Proteins/analysis , Humans , Immunohistochemistry , Middle Aged , PrognosisABSTRACT
Introducción.La vulva puede ser asiento de diversos tumores malignos, de los cuales el más frecuente es el espinocelular; sin embargo, los tumores vulvares no espinocelulares son de gran importancia debido su mal pronóstico.Objetivos. Determinar la forma de presentación clínica, sintomatología, variedad histopatológica y el estadio de los tumores vulvares no espinocelulares al momento de la consulta. Evaluar el rol del dermatólogo en el diagnóstico y seguimiento de estos pacientes. Métodos. Se realizó un estudio retrospectivo, observacional y analítico de pacientes que concurrieron por derivación al consultorio de Patología Vulvar desde agosto de 2002 a agosto de 2010. Se evaluaron las historias clínicas y los archivos anatomopatológicos e iconográficos delos tumores vulvares no espinocelulares. Resultados. De un total de 637 consultas por derivación en el consultorio de patología vulvar, el 9,1% (n=56) correspondió a tumores malignos. De éstos, el 76,78% (n=43) fueron carcinoma espinocelular (incluidos neoplasia intravulvar y carcinoma invasor) y el 23,22% (n=15), carcinoma no espinocelular. Del total de estos últimos, ocuparon en orden de frecuenta decreciente: tumores secundarios de otros órganos, enfermedad de Paget extramamaria, melanoma, adenocarcinoma de la glándula de Bartolino y sarcoma. El motivo de consulta más frecuente fue dolor, y la forma clínica de presentación fue lesión exofítica única. Conclusiones. Destacamos la alta incidencia de tumores vulvares no espinocelulares en nuestro medio: representa el 23,2% de las neoplasias vulvares, en comparación con la literatura, que es del 10%.
Background. The vulva may be the seat of many malignancies, of which the most common is squamous-cell carcinoma; nevertheless non squamous-cell vulvar neoplasms are significant because of their poor prognosis. Objectives. To determine the symptoms, clinical presentation and stage of the disease at thetime of consultation. To establish associations with various risk factors and evaluate prognosis. Toasess the role of the dermatologist in the appropriate diagnosis and monitoring of these patients.Methods. We performed a retrospective and observational study of patients seen at a vulvar-disease Clinic from August 2002 to August 2010. We reviewed the clinical records, biopsy specimens and iconographic files.Results.From a total of 680 consultations to a vulvar-disease Clinic 7% (n=48) corresponded to malignant tumors. Of these 73% (n=35) were squamous-cell carcinomas and 27% (n=13) were non-squamous-cell carcinomas, which in decreasing order of frequency, were: secondarytumors from other organs, extramamammary Pagets disease, melanoma, adenocarcinoma andsarcoma. The most frequent cause of consultation was pain, and the clinical presentation was a single exophytic lesion.
Subject(s)
Female , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/etiology , Vulvar Neoplasms/therapy , Bartholin's Glands , Bartholin's Glands/pathology , Melanoma , Paget Disease, Extramammary , Prognosis , RhabdomyosarcomaABSTRACT
We have analyzed the predictive/prognostic value of Bcl-2 protein in breast cancer patients treated with neoadjuvant chemotherapy. One hundred and ten patients were submitted to two different chemotherapeutic regimens: a) 5-fluorouracil, adriamycin or epirubicin, and cyclophosphamide (FAC/FEC) during 2-6 cycles before surgery and 3 or 4 additional cycles of FAC/FEC after surgery (n=40) and b) doxorubicin (D) 75 mg/m(2) or epirubicin (E) 120 mg/m(2) during 4 cycles before surgery, and 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) after surgery (n=70). Bcl-2 expression, evaluated by immunohistochemistry, did not change significantly after chemotherapy and was not related to clinical/pathological response. In FAC/FEC group, Bcl-2 positive expression after chemotherapy correlated with better disease free survival (DFS) and overall survival (OS) (P=0.008 and P=0.001). In D/E group, Bcl-2 also correlated with better DFS and OS (P=0.03 and P=0.054) in the post-chemotherapy biopsies. An unusual nuclear localization of Bax was observed in some biopsies, but this localization did not correlate with the tumor response or outcome of the patients. We found that a high Bcl-2 expression had no predictive value but had prognostic value in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy.
