Expression of estrogen receptor beta in the breast carcinoma of BRCA1 mutation carriers

<p>Abstract</p> <p>Background</p> <p>Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Nevertheless, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ERβ, raised a question of its role in hereditary breast cancer. The aim of this study was to assess the frequency of ERα, ERβ, PgR (progesterone receptor) and HER-2 expression in breast cancer patients with mutated <it>BRCA1 </it>gene and in the control group.</p> <p>Methods</p> <p>The study group consisted of 48 women with <it>BRCA1 </it>gene mutations confirmed by multiplex PCR assay. The patients were tested for three most common mutations of BRCA1 affecting the Polish population (5382insC, C61G, 4153delA). Immunostaining for ERα, ERβ and PgR (progesterone receptor) was performed using monoclonal antibodies against ERα, PgR (DakoCytomation), and polyclonal antibody against ERβ (Chemicon). The EnVision detection system was applied. The study population comprised a control group of 120 BC operated successively during the years 1998–99.</p> <p>Results</p> <p>The results of our investigation showed that <it>BRCA1 </it>mutation carriers were more likely to have ERα-negative breast cancer than those in the control group. Only 14.5% of <it>BRCA1</it>-related cancers were ERα-positive compared with 57.5% in the control group (<it>P </it>< 0.0001). On the contrary, the expression of ERβ protein was observed in 42% of <it>BRCA1</it>-related tumors and in 55% of the control group. An interesting finding was that most hereditary cancers (75% of the whole group) were triple-negative: ERα(-)/PgR(-)/HER-2(-) but almost half of this group (44.4%) showed the expression of ERβ.</p> <p>Conclusion</p> <p>In the case of <it>BRCA1</it>-associated tumors the expression of ERβ was significantly higher than the expression of ERα. This may explain the effectiveness of tamoxifen in preventing contralateral breast cancer development in <it>BRCA1 </it>mutation carriers.</p

Paraneoplastic syndromes in gynecologic cancers

Paraneoplastic syndromes (PS) involve signs and symptoms from various organs, which accompany tumors at various stages of their development: they may precede the development of cancer by a few months or even years, may be detected during the diagnosis or treatment of a malignant tumor, or they may precede its relapse following treatment. The most frequent mechanism of their development is thought to involve disturbances in the endocrine or autoimmune system, due to the hormones secreted by the tumors, their precursors or cytokines (secretion of ADH, PTHrP, PTH, ACTH, IL-1, IL-6, TNF). Immune mechanisms result in the development of antibodies specific for antigens of own healthy tissues, e.g. in neurologic PS antibodies are detected which are specific for Yo, CV2 and Ri. Among many types of PS in tumors of female genital organs, the most frequent ones involve endocrine syndromes leading to hormonal dysregulation, neurologic ones which result in occasionally severe disturbances of the central nervous system, hematologic PS, the most common one being thromboembolic lesions, and dermatological PS. The other PS found in early and, more frequently, in more advanced cancer include the syndrome of neoplastic cachexia, sometimes encountered in ovarian and cervical cancer.Zespoły paranowotworowe (ZP) są to objawy ze strony różnych tkanek i narządów, towarzyszące nowotworom na różnych etapach ich rozwoju. Mogą wyprzedzać o kilka miesięcy lub nawet lat rozwój raka, mogą być stwierdzane w czasie diagnostyki lub leczenia nowotworu złośliwego, a także wyprzedzać jego nawrót po leczeniu. Za najczęstszy mechanizm ich powstawania uważa się zaburzenia w układzie endokrynnym lub autoimmunologicznym. Mechanizm endokrynny polega na wydzielaniu przez guz hormonów, ich prekursorów lub cytokin (ADH, PTHrP, PTH, ACTH, IL-1, IL-6, TNF). W wyniku mechanizmów immunologicznych dochodzi do powstania przeciwciał przeciwko antygenom własnych zdrowych tkanek, na przykład w ZP neurologicznych stwierdza się przeciwciała anty-Yo, anty-CV2 i anty-Ri. Wśród wielu zespołów paranowotworowych występujących w przebiegu nowotworów narządów płciowych kobiet najczęściej obserwuje się zespoły endokrynologiczne, prowadzące do dysregulacji hormonalnej, neurologiczne, w wyniku których stwierdza się niekiedy ciężkie zaburzenia ze strony ośrodkowego układu nerwowego, hematologiczne, spośród których najczęstsze są zaburzenia zatorowo-zakrzepowe, oraz ZP dermatologiczne. Do innych ZP związanych między innymi z odżywianiem i metabolizmem zalicza się zespół wyniszczenia nowotworowego, stwierdzany w przebiegu zaawansowanego raka jajnika i szyjki macicy