Kourounis G

Inheritance and perinatal consequences of inherited thrombophilia in Greece

To investigate the impact of inherited thrombophilic factors on the gestational outcome of unselected pregnant women.

Successful pregnancy outcome in a patient with primary Addison's disease

A 32-year-old primigravida with primary Addisons disease was followed up from the early stages of pregnancy to delivery and puerperium by a multidisciplinary medical board. Besides fetal surveillance, great attention was given to steroid replacement therapy in order to avoid complications. Vaginal labor resulted in the birth of a healthy neonate that performed well.

A clinicopathologic study on patients with endometrial cancer after adjuvant tamoxifen treatment for breast cancer: a single center experience.

To the Editor: Tamoxifen (TAM) is a nonsteroidal, selective estrogen receptor (ER) modulator that has potent anti-estrogenic activity in the breast while displaying weak estrogen activity in the endometrium. It is the hormonal treatment of choice for postmenopausal breast cancer patients with positive ER over the past two decades and its use has been convincingly shown to improve the disease-free survival as well as overall survival (1). One of the most significant and deleterious side effects of TAM treatment in postmenopausal women with breast cancer appears to be its proliferative effect on the endometrium. Overall endometrial pathologies, including hyperplasia, polyps, carcinoma and sarcoma have been identified in up to 36% of postmenopausal breast cancer TAM-treated patients. The frequency of these endometrial pathologies was found to be significantly higher among postmenopausal breast cancer TAM-treated patients, compared with postmenopausal breast cancer non-TAM-treated patients (2–4). It was also found to be more common among healthy women who receive preventive TAM treatment, compared with healthy non-TAM-treated women (5). The pathogenic mechanism for the development of TAMassociated malignant endometrial tumors has not yet been clearly defined. The Stockholm Trial showed a continued divergence of the cumulative incidence curves of endometrial cancer for the TAM-treated and control groups even several years after cessation of TAM treatment (6). Many other reports published in recent years have demonstrated a significant positive association between longer duration of TAM treatment and the appearance of endometrial cancer. The relative risk (RR) for endometrial cancer, when compared with non-TAMtreated patients, with gradual increase in duration of TAM treatment, is increasing up to 60 consecutive months (7). It has been synonymously reported that endometrial pathologies are associated with high cumulative doses of TAM administered to postmenopausal breast cancer patients. Women who received 20 mg of TAM daily developed endometrial pathologies after longer periods of treatment compared to those who were treated with 40 mg of TAM daily (8). During the last decade efforts have focused on attempting to identify cytokinetic or molecular events that correlate with the malignant potential of endometrial cancers. Several investigators have evaluated the expression of oncogenes and tumor suppressor genes. Furthermore indicators of cell proliferation have been evaluated. Estrogen stimulates cellular proliferation regulated by the ER, whereas progesterone inhibits cellular growth and induces differentiation regulated by the progesterone receptor (PR). It is well recognized that ER and PR are important prognostic factors for zendometrial carcinoma. High levels of ER and PR are directly correlated with a lower tumor grade, less myometrial invasion and a lower incidence of lymph node metastases (9). Members of the human epidermal growth factor receptor family (HER) of receptor tyrosine kinases play a critical role in both development and oncogenesis. The latter is suggested by the frequent overexpression of HER-2, EGFR, HER-3 and HER-4 in a wide variety of tumors including breast, colorectal, ovarian, and non-small cell lung cancers. The biological activities of the HER family are exerted through various ligandreceptor and receptor-receptor interactions. One receptor that plays a central role in this signaling network is HER-2/Neu (cerb2), which is considered the preferred heterodimerization partner for other members of the HER family and responsible for regulating cell growth and differentiation (10). Ki-67 is a marker of cell proliferation. It is expressed in the nucleus of cells that are actively undergoing cell proliferation (i.e., not in G0 or early G1) (11). The balance between cell proliferation Address correspondence and reprint requests to: Dimitrios M. Kardamakis, Department of Radiotherapy, University of Patras Medical School, 26500 Rion, Patras, Greece, or e-mail: kardim@med.upatras.gr