also known as chromosome region maintenance 1 (CRM1) protein, is involved in the homeostatic of nucleocytoplasmic transport of over 200 known cargos, most of them are tumor suppressor and cell cycle regulatory proteins such as p53, pRb, FOXOs, BRCA1/2 and inhibitor of NF-κB (Kau et al., 2004; Abstract Objectives: Exportin 1(XPO1), a nuclear exporter protein, has been gaining recognition in cancer progression and treatment. This study aimed to evaluate the association between the overexpression of XPO1 with NF-κB, Ki67 and clinicopathological characteristics in colorectal cancer (CRC) tissue samples and to explore the anti-proliferative effect of KPT-330, as XPO1 inhibitor, in colorectal cancer cell line. Methods: Forty CRC tissue samples were analyzed by immunostaining for the expressions of XPO1, NF-κB and Ki67 and then the anti-proliferative effect of the KPT-330 was also evaluated in HT29 colorectal cancer cell line. Results: XPO1 overexpression was observed in 52.5% of CRC and significantly apparent with strong intensity in tumor cells compared to the normal adjacent epithelium (P<0.001).Regarding to the histopathological characteristics, the XPO1 overexpression significantly associated with advanced tumor stages (P=0.049) and has great tendency towards moderate/poorly differentiated tumors. Although the XPO1 overexpression was strongly associated with high Ki67 expression (P=0.001), only Ki67 expression showed significant association with tumor size (P=0.012). No significant association was detected between the XPO1 overexpression and NF-κB, while the NF-κB positive expression was significantly associated with lymph node metastasis and Ki67 expression at P=0.027 and P= 0.007, respectively. The in vitro experiments showed a great impact of KPT-330, as XPO1 inhibitor, to inhibit cancer growth in dose and time dependent manner and significantly diminished the colony formation (P<0.001) of HT29 cells-associated with the expression of Ki67 (P<0.001). Conclusion: XPO1 overexpression and NF-κB expression may serve as potential biomarker associated with CRC pathogenesis and proliferation, while the KPT-330 is effectively inhibited-colon cancer growth in vitro. Further studies considering the prognostication role of XPO1 overexpression in CRC are required.

The steroid hormone receptor (SR) profile was determined for both the estrogen receptor (ER) and progesterone receptor (PR) in 55 fibroadenomas, 69 fibrocystic changes, 38 ordinary, and 14 atypical intraductal hyperplasias as well as 149 breast carcinomas obtained from 325 female patients by diagnostic surgical biopsy. Normal breast tissue adjacent to the lesions under study was simultaneously evaluated in 234 cases. SR were proven immunohistochemically in cryostat sections using an immunohistochemical assay with rat monoclonal antibodies against human ER or PR. The findings were scored and summarized into the phenotypes ER+PR+,ER−PR+, ER+PR− and ER−PR−. The ER+PR+ status was most often found in fibroadenomas (67%) and normal breast tissue (64%) as well as in fibrocystic changes (63%) and breast carcinomas (58%). ER−PR− was inversely rare in fibroadenomas (4%), normal breast tissue (15%), fibrocystic changes (23%), and breast carcinomas (29%). The simultaneous SR analysis in breast disease and its surrounding normal tissue showed in fibroadenomas in 90% and in fibrocystic changes in 80%, a ER/PR phenotype expression similar to adjacent normal tissue; whereas in breast carcinomas the SR status corresponded with the preexisting normal tissue only in 36%. The comparative SR analysis of normal and pathological breast tissue showed a gradually inverse biological correlation between the decrease of ER+PR+ and the increase of ER−PR− frequency from benign breast changes to noninvasive and invasive breast carcinomas. In benign breast epithelium, ER−PR+ might be regarded as low‐risk phenotype, whereas ER+PR− could be estimated as high‐risk phenotype in view of a later dedifferentiation and possible malignization. The more frequent discordance of SR expression between breast carcinomas and their adjacent normal breast tissue suggests that the neoplastic growth may become more and more independent from normal endocrine influences.