Changes in biologic features between primary and recurrent or relapsed breast cancers

Changes in ER, PR and Her2 receptor status between primary and metastatic cancer tissue have been suggested in breast cancer. The frequencies of these changes are still not fully understood. The purpose of this study was to evaluate these changes in breast cancer population of Kuwait. Changes in the biological features between primary and recurrent disease in 70 patients who presented between 2009 and 2012 was studied. Statistical comparisons between groups was done using chi square test while Kaplan Meier method was used to perform analysis of survival after relapse. All analysis was carried out using the IBM-SPSS statistical software. There was a decrease in ER and PR positivity from 61.4% to 58.6% and 61.4% to 44.3% respectively. The overall change in ER and PR status was 28.5% and 25.7% respectively. There was an increase in the Her2 positivity as the tumor relapsed and overall changes were seen in 5.7% of cases. Patients with breast cancer experience change in biological markers through the course of their disease. The changes are more with hormone receptors compared to Her2. Re-biopsy should be considered at relapse if feasible

Expression of JMJD2A in infiltrating duct carcinoma was markedly higher than fibroadenoma, and associated with expression of ARHI, p53 and ER in infiltrating duct carcinoma.

Jumonji Domain Containing 2A (JMJD2A) may be a cancer-associated gene involved in human breast cancer. With a view to investigating expression of JMJD2A in human breast cancer and benign lesion tissues as well as relationship between JMJD2A and tumor related proteins, histological and immunohistochemical analysis, Western blot and quantitative real-time PCR in infiltrating duct carcinoma and fibroadenoma for JMJD2A and immunohistochemical analysis and quantitative real-time PCR in infiltrating duct carcinoma for tumor related proteins (ARHI, p53, ER, PR and CerbB-2) were performed. Histological examination validated the clinical diagnosis. The JMJD2A positive rate of infiltrating duct carcinoma was significantly higher than fibroadenoma by immunohistochemical analysis. The mean optical density of JMJD2A in infiltrating duct carcinoma was higher than fibroadenoma by western blot. JMJD2A mRNA level in infiltrating duct carcinoma was higher than fibroadenoma by quantitative real-time PCR. Spearman correlation analysis revealed that the expression of JMJD2A was associated with ARHI, p53 and ER from immunohistochemical results respectively. Pearson correlation analysis revealed that the expression of JMJD2A was associated with ARHI, p53 and ER from quantitative real-time PCR results respectively. Expression of JMJD2A in infiltrating duct carcinoma was higher, and associated with ARHI, p53 and ER. The results may take JMJD2A as a potential diagnostic and therapeutic target in human breast cancer.

Expressão da proteína erbB-2 e dos receptores de hormônios na transição das regiões in situ para invasora de tumores da mama / ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma

OBJETIVOS: avaliar a expressão de erbB-2 e dos receptores hormonais para estrógeno e progesterona (RE/RP) nas regiões de transição entre as frações in situ e invasoras de neoplasias ductais da mama (CDIS e CDI, respectivamente). MÉTODOS: oitenta e cinco casos de neoplasias mamárias, contendo regiões contíguas de CDIS e CDI, foram selecionados. Espécimes histológicos das áreas de CDIS e de CDI foram obtidos através da técnica de tissue microarray (TMA). As expressões da erbB-2 e dos RE/RP foram avaliadas por meio de imunoistoquímica convencional. A comparação da expressão da erbB-2 e dos RE/RP nas frações in situ e invasoras da mama foi realizada com emprego do teste de McNemar. Os intervalos de confiança foram determinados em 5 por cento (p=0,05). Foram calculados coeficientes de correlação intraclasse (ICC) para avaliar a concordância na tabulação cruzada da expressão de erbB-2 e RE/RP nas frações de CDIS e CDI. RESULTADOS: a expressão da erbB-2 não diferiu entre as áreas de CDIS e CDI (p=0,38). Comparando caso a caso suas áreas de CDIS e CDI, houve boa concordância na expressão da erbB-2 (coeficiente de correlação intraclasse, ICC=0,64), dos RP (ICC = 0,71) e dos RE (ICC = 0,64). Considerando apenas tumores cujo componente in situ apresentasse áreas de necrose (comedo), o ICC para erbB-2 foi de 0,4, comparado a 0,6 no conjunto completo de casos. Os ICC não diferiram substancialmente daqueles obtidos com o conjunto completo de espécimes em relação aos RE/RP: para RE, ICC=0,7 (versus 0,7 no conjunto completo), e para RP, ICC=0,7 (versus 0,6 no conjunto completo). CONCLUSÕES: nossos achados sugerem que as expressões de erbB-2 e RE/RP não diferem nos componentes contíguos in situ e invasivo em tumores ductais da mama.

PURPOSE: to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). METHODS: Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5 percent (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. RESULTS: the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). CONCLUSIONS: our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.

Adrenocorticotropic hormone production in breast cancer.

Presence of adrenocorticotropic hormone (ACTH) was investigated in tissues from 150 cases of primary breast cancer. ACTH peptides were detected in 16.7% cases and ACTH expression was higher in post-menopausal cancers. A significant association was noticed between the presence of ACTH and the positive estrogen receptor (ER) status of tumors. The study indicated a probable role of these ectopic ACTH peptides in steroid hormone related pathology of breast cancer.

The relationship of the expression of estrogen receptor in cartilage cell and osteoarthritis induced by bilateral ovariectomy in guinea pig / 华中科技大学学报（医学）（英德文版）

To investigate the estrogen receptor (ER) expression in cartilage cell in the development of osteoarthritis induced by bilateral ovariectomy in guinea pig and to find their relationship. 30 two-month-old female guinea pigs were randomly divided into two groups (n = 15 each): sham operation (control) group and ovariectomized group (OVX); Scanning electorne microscope (SEM) and transmission electron microscope (TEM) were obtained to analysis the cartilage degeneration of the hind limb knee joint after 6 and 12 weeks of ovariectomy. Dextran-Coated-Charcoal (DCC) was taken to quantitively detect the expression of ER. The serum levels of estrogen and gestone were detected by immune contest assay. The results showed that ER do exist in the cartilages of the guinea pigs, with higher expression in the control group than in OVX group at the same time point (P < 0.05). It was increased also at 12 th week after operation than that of preoperation. The blood serum levels of estrogen and gestone showed a similar tendency to the expression of ER. Joint cartilage degeneration detected by SEM and TEM could be found at 6 th week, but severe degenerative lesions at 12 th week in the OVX group compared with the control group (P < 0.01). The data suggested that bilateral ovariectomy in guinea pig lead to severe osteoarthritis which mighgt be related to the lower serum level of estrogen and the downregulation of the expression of ER in the cartilage also.

Overexpression of c-erbB-2 oncoprotein and associated pathobiological factors in invasive primary breast cancer.

Breast cancer tissues from 271 cases were analyzed immunologically for c-erbB-2 oncoprotein (HER-2/neu), epidermal growth factor receptor (EGF-R) and estrogen receptor (ER). Overexpression of both c-erbB-2 oncoprotein and EGF-R showed an inverse association with ER and a direct association with metastatic involvement of lymph node and high histological grade. The frequency of c-erbB-2 and EGF-R overexpression was significantly higher among postmenopausal cases in comparison with premenopausal cases. Further, only in postmenopausal patients, c-erbB-2 oncoprotein (chi2 = 6.4, P < 0.05) and EGF-R (chi2 = 6.4, p < 0.05) as well as their concomitant expression (chi2 = 11.5, p < 0.01) revealed a statistically significant association with ER.

Expression of progesterone receptor in human keratinocytes

Despite the various responses of human skin to female sex hormones, cellular and subcellular targets and the mechanisms of action of estrogen and progesterone in human skin are not well understood. The detection of estrogen receptor (ER) and progesterone receptor (PR) in the skin is of great importance to understand the effect of estrogen and progesterone. In primary cultures of human keratinocytes, expression of ER and PR was monitored by immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Paraffin embedded skin tissues were stained with monoclonal antibodies to human ER and PR by immunohistochemistry. Cultured human keratinocytes expressed cytoplasmic PR protein and PR mRNA transcripts. By contrast, ER was detected only at the mRNA level. Suprabasal keratinocytes from samples of pruritic urticarial papules, plaques of pregnancy (PUPPP) and psoriasis were stained positively only for PR, while those from samples of erythema nodosum were negative for both ER and PR. Lesional epidermis of PUPPP showed positive PR immunoreactivity, while nonlesional epidermis did not. No other cells in the normal human skin were stained with ER and PR. The present study suggests that by expressing PR human keratinocytes act as targets for progesterone action.

El receptor de estrógenos y la glándula mamaria / Estrogen receptors and the mammary gland

Desde hace varias décadas se sabe que las hormonas esteroides, como la progesterona y el estradiol, son importantes en la regulación de algunos genes involucrados en los procesos de crecimiento, proliferación y diferenciación de las células de la glándula mamaria en diferentes especies animales y en el humano. La presencia o ausencia del receptor de estrógenos es utilizado en la clínica como un marcador de malignidad, evaluación pronóstica, o como parámetro de decisión para el tratamiento con antiestrógenos de algunos tipos de cáncer dependientes de hormonas en la glándula mamaria. La presente revisión tiene por objeto el mostrar algunos de los avances en el conocimiento de la estructura del receptor y su interacción con protooncogenes y factores de crecimiento. Por último, se hace referencia a la relación que tiene la presencia de este receptor en la fisiopatología del cáncer de mama