ABSTRACT
Breast cancer is a major public-health issue worldwide. It is the most common cancer in women constituting 22% of all cancer cases world wide. Until recently, breast cancer was subclassified on the basis of cellular morphology and the presence of several receptors, namely ER, PgR, and the Her2, identified by immunohistochemistry. The present study was designed aiming to determine the expression of P-glycoprotein in infiltrating ductal carcinoma [IDC] patients, to correlate the expression of P-glycoprotein with other clinical and pathological parameters and to ascertain whether pretreatment detection of P-glycoprotein in patients with breast cancer could be utilized as a reliable predictor of poor prognosis. The present study constituted thirty nine cases of IDC received at the pathology department during one year beginning at January 2004. For all studied cases, routine histopathologic diagnosis and immunodetection of P-gp, ER, PgR and Her2 were carried on. Retrospective follow up of the patients for period of 2-3 years after the mastectomy operation was carried on with statistical analysis of the results. ER positive status was encountered in 10 cases [25%]. PgR positive status was encountered in 14 cases [35.9%]. A statistically significant association was detected between both ER and PgR expression and nuclear grade [P=0.002, p=0.017]. Her 2 positive immunostaining was detected in 12 cases [30.8%]. P-gp was detected in 26 cases [66.7%]. Statistically significant association between P-gp and Her2 expression was found [p=0.027]. The present study detected that ER negativity [p=0.009], nuclear grade III [P=0.06] and triple-negative molecular subtype [P=0.017] were associated with poor local recurrence-free survival [LRFS]. Her2 positivity [P=0.06] and lymph node metastasis [P=0.08] were associated with poor distant-metastasis free survival [DMES]. Her2/neu IDC that express P-gp had the poorest DFS. Pretreatment detection of P-gp is of great value to predict the response to chemotherapy in patients with Her2 -positive and triple negative infiltrating ductal carcinomas
Subject(s)
Humans , Female , Breast Neoplasms/immunology , Carcinoma, Ductal, Breast , ATP Binding Cassette Transporter, Subfamily B, Member 1/blood , Immunohistochemistry , Prognosis , Receptors, Estrogen , Receptors, Progesterone , Neoplasm Recurrence, Local , Disease-Free SurvivalABSTRACT
La Glicoproteína P (Gp-P) es una proteína transmembranaria con función transportadora, que tiene por misión expeler xenobióticos lipofilíticos. Esta glicoproteína tiene una distribución específica y unos niveles de expresión variables en las células sanguíneas humanas encargadas de la defensa en el organismo. El objetivo de este trabajo fue comparar y establecer si son reproducibles los resultados obtenidos por dos laboratorios distintos en la valoración de la expresión de glicoproteína P (Gp-P) en muestras celulares con baja expresión de esta glicoproteína, como es el caso de las células de sangre periférica. Se valoraron las subpoblaciones celulares de ciento veinticinco (125) muestras de sangre periférica de individuos sanos por citometría de flujo e inmunofluorescencia directa, utilizando el anticuerpo monoclonal JSB-1 conjugando con isotiocianato de fluoresceína (FITC), en dos citómetros de flujo de la misma marca y modelo, situados en dos laboratorios diferentes: Departamento de Anatomía Patológica, Facultad de Medicina, Universidad de Granada y Centro de Transfusión Sanguínea de Granada, España. Los resultados demostraron que la mejor correlación estadística del porcentaje de Positividad (por ciento POS) fue observada en los linfositos (r=0.93), mientras que para la Incorporación Media Fluorescencia Específica (IMFE) se observó en los granulocitos (r=0.94). Los resultados obtenidos con la metodología empleada en la determinación de Gp-P por citometría de flujo e inmunofluorescencia directa, permiten concluir que es una técnica reproducible y fiable para la evaluación del fenómeno de Resistencia Multiple a Drogas (MDR) en las subpoblaciones celulares normales de sangre periférica
Subject(s)
Humans , Flow Cytometry , Leukocytes , ATP Binding Cassette Transporter, Subfamily B, Member 1/blood , Blood Specimen Collection , Medicine , VenezuelaABSTRACT
Cervical cancer patients have a defective immune system. There is a decrease of total white blood cell count including lymphocytes and natural killer (NK) cells. NK cells, one type of lymphocytes, play a role to eliminate cancer cells by antibody dependent cell mediated cytotoxicity (ADCC) mechanism. Previous studies have shown that P-glycoprotein (170 kDa, transmembrane protein) may be a transporter for cytokine releasing in ADCC mechanism. This study proposed to explore the role of bitter melon intake in cervical cancer patients undergoing normal treatment (radiotherapy). Subjects were divided into three groups: 1) normal control (women 35-55 years, n = 35), 2) patient control (n = 30) and 3) patient treatment (n = 30) groups. Patient control and patient treatment groups were cervical cancer patients (stage II or III) treated with radiotherapy (without or with bitter melon ingestion). Blood samples of patient control and patient treatment groups were analyzed for NK cells percentage and P-glycoprotein level. Bitter melon is a Thai herb. Previous studies have shown that bitter melon can stimulate lymphocyte activity in vitro and in vivo (mouse). The authors hope that bitter melon could stimulate the increase of NK cells percentage and P-glycoprotein level on the membrane in blood samples from cervical cancer patients who ingest bitter melon. The results showed an increased percentage of NK cells in patient control and patient treatment groups. The increase in each group is significant (p < 0.05) when compared with the percentage of NK cells from second and third blood sampling time (after radiation with of without bitter melon intake for 45 and 90 days) with first blood sampling time (before treatment). The results also show a significant decrease of P-glycoprotein level (p < 0.05) in second and third blood sampling times when compared with first blood sampling time of the patient treatment group. There was no significant difference of P-glycoprotein (P-gp) level from first, second and third blood sampling times in patient control group. Bitter melon ingestion did not affect NK cell level but it affected the decrease of P-gp level on NK cell membrane.