Association Of Hormone Receptor Research Articles

Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan

BackgroundBreast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.MethodologyA cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.ResultsOne hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40–50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.ConclusionIn our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.

Predictors of pathologic response and correlation with long-term outcomes in a trial of neoadjuvant concurrent paclitaxel radiation in locally advanced breast cancer (LABC).

589 Background: The association of hormone receptor (HR) status of the original tumor with pathologic response and correlation with DFS and OS from a multi-institutional trial of concurrent paclitaxel (P) and radiation (RT) are reported. Methods: 105 LABC patients were treated with neoadjuvant concurrent P and RT (P: 30 mg/m2 2x/week for 10-12 weeks; RT: 1.8 Gy daily to breast, axillary and supraclavicular LN weeks 2-7 to total of 45 Gy followed by a tumor boost of 14 Gy at 2 Gy/fraction). Pathologic response was defined as absence of invasive cancer in breast and LN (pCR) or persistence of less than 10 microscopic foci of invasive cancer in breast or LN (pPR). Logistic regression methods were used to predict response status, logrank tests and Cox proportional hazards methods to evaluate DFS and OS in relation to HR status and pathologic response. Results: Pathologic response (pCR+pPR) for the entire cohort was achieved in 36/105 patients (34%, 95% CI: 25-44%). For all patients, lack of a pathologic response conveyed 4.4 times greater death rate than for pathologic responders (95% CI 1.5-12.7). Nonresponders have a median survival time of 84 months; median not reached for responders. A significantly greater rate of pathologic response occurred in patients with HR negative cancers compared with HR positive cancers (p < 0.001): 54% (95% CI 39-69%) compared to 18% (95% CI of 9-30%). HR status was the only predictor of pathologic response after concurrent P-RT. As expected, HR negative tumors had a worse prognosis than HR positive ones; this feature remained despite the achievement of a pathologic response. However, pathologic response and HR status jointly predicted DFS (likelihood ratio p < 0.001). The clinical benefit from achieving a pathologic response was most pronounced in patients with HR negative tumors with a reduction in recurrence or death rate of 75% as compared with HR negative nonresponders. Conclusions: Conclusions: HR status is highly predictive of response to neoadjuvant concurrent paclitaxel and radiation; more than half of the patients with HR negative tumors achieved a pathologic response, which translates into superior DFS and OS. No significant financial relationships to disclose.

Correlation between Epidermal Growth Factor Receptor Mutations and Expression of Female Hormone Receptors in East-Asian Lung Adenocarcinomas

Epidermal growth factor receptor (EGFR) mutations are more common in lung adenocarcinoma and in female patients of East-Asian origin. We aimed to assess the expression of female hormone receptors in East-Asian lung adenocarcinomas, their correlation with EGFR mutations, and prognostic significance. Estrogen receptor (ER)alpha, ERbeta, progesterone receptor (PR), and Her-2 expression were examined using immunohistochemical methods on 109 lung adenocarcinoma cases. EGFR mutations were analyzed by partially denaturing high performance liquid chromatography. Association of hormone receptor with clinical factors was assessed using the Fisher's exact test. Associations with survival were assessed using the Cox proportional hazard model. Using scoring criteria routinely used for breast cancer, there were four (4%) ERalpha, one (1%) ERbeta, six (6%) PR, and one (1%) Her-2 positive cases. Considering any staining as positive, 14 (14%) ERalpha, 10 (9%) ERbeta, 12 (12%) PR, and 26 (24%) Her-2 cases were positive. Thirty-nine patients (39%) had EGFR mutations. ERalpha positivity was significantly associated with ERbeta and PR positivity. There were more EGFR mutations seen in tumors with ERbeta positivity (60%) compared with those with negative expression (37.9%), and there was a trend toward a poorer outcome for patients with tumor that were positive for ERbeta and Her-2. We found that ERalpha, ERbeta, PR, and Her-2 expression in lung adenocarcinoma are present but limited. This suggests that hormonal influence may not be an important factor to account for the high prevalence of lung cancer among the East-Asian women.

Zinc(II) Inhibits the Release of Thyroid and Glucocorticoid Receptors from Chromatin of Cultured GC Cells

The effect of Zn(II) on the association of thyroid and glucocorticoid hormone receptors with chromatin was studied in chromatin from cultured GC cells. Chromatin was incubated at 0-4 degrees C in 20 mM Tris, pH 7.4. When buffers contained 0.15 M NaCl, the release of T3 receptors from chromatin was time-dependent; 50% of T3 receptors were released after 30 min incubation. Receptor release appeared relatively specific since less than 10% of chromatin protein and DNA, and less than 13% of chromatin zinc were released under these conditions. Addition of Zn(II) inhibited receptor release; one-half maximal inhibition occurred at 1 microM ZnCl2. Cd(II) and to a lesser extent Co(II) had similar but smaller effects. Addition of EDTA prevented this effect of Zn(II); EDTA alone enhanced receptor release. Zn(II) also inhibited the release of glucocorticoid receptors from chromatin in similar incubations. Our findings suggest that Zn(II) increases the association of hormone receptors with chromatin and, thereby, may influence receptor function.

Peptide mapping of intersubunit and receptor interactions of human choriogonadotropin

Seven peptides covering the entire sequence of human choriogonadotropin (hCG) α-subunit, eight peptides covering the hCG β-subunit sequence and two peptides, one of human β-lutropin and one of β-thyrotropin were synthesized. We checked their ability to prevent reassociation between hCG α- and β-subunits and between hCG and its receptor. Only the α1–22, α59–92 and β1–16 peptides inhibited the reassociation between the α- and β-subunits of hCG with an ED 50 of respectively 2 mM, 2 mM and 4 mM. Using porcine Leydig cells in primary culture, we showed that α33–59, α41–59 and β1–16 peptides decreased both the specific binding to the cell surface and the intemalization of [ 125I]hCG and [ 125I]porcine LH with ED 50 of 0.3, 0.1 and 0.5 mM, respectively. From these results, the following minimal area may be assigned, (i) to the α−β interaction: α5−16, α52–72 (or α59–70) and β8–16, and (ii) to the hormone-receptor association: α41–45 and β8–16.

Expression and characterization of erythropoietin receptors on normal human bone marrow cells

We studied the specific binding of 125I-labeled bioactive recombinant human erythropoietin (Epo) to human bone marrow mononuclear cells (BMNC) obtained from normal subjects. The 125I-labeled Epo bound specifically to the BMNC. Scatchard analysis of the data showed two classes of binding sites; one high affinity (Kd 0.07 nM) and the other low affinity (Kd 0.38 nM). The number of Epo binding sites per BMNC was 46 +/- 16 high-affinity receptors and 91 +/- 51 low-affinity receptors. The specific binding was displaced by unlabeled Epo, but not by other growth factors. Receptor internalization was observed significantly at 37 degrees C, but was prevented by the presence of 0.2% sodium azide. These findings indicate that human BMNC possess two classes of specific Epo receptors with characteristics of a hormone-receptor association.

The erythropoietin receptor of rat erythroid progenitor lens. Characterization and affinity cross-linkage.

Commercially available 125I-labeled erythropoietin, obtained by genetic engineering from a human gene, was used to characterize receptors for this hormone on the cell surface of rat erythroid progenitor cells. A low number of high affinity binding sites (487 +/- 32 sites/cell, Kd = 167 +/- 14 pm) were found. Nonerythroid cells and erythrocytes did not exhibit specific binding. The high affinity binding was reversible and displaced by unlabeled erythropoietin, but not by other hormones and growth factors. After incubation at 37 degrees C, nearly 35% of the specifically bound erythropoietin seemed to be internalized, as judged by resistance to acidic buffer treatment. Thus, binding showed characteristics of a hormone-receptor association. 125I-Erythropoietin-labeled cells were treated with the bifunctional reagent dissucinimidyl suberate. Analysis of the cellular extracts by polyacrylamide gel electrophoresis under denaturing and reducing conditions revealed that erythropoietin can be cross-linked to two molecules of 94 and 78 kDa, respectively. Both labeled bands disappeared when the cells were labeled in the presence of an excess of unlabeled erythropoietin. Under nonreducing conditions, a cross-linked band of 230-255 kDa was observed. The relationships between these bands are discussed.

Evidence for synergism in steroid hormone-receptor association

A number of glucocorticoids stimulated oestradiol binding to liver cytosol receptor; oestradiol activated glucocorticoid receptor association at a time when it reversed triamcinolone mediated increase in liver glycogen synthesis.