Expression of metastases-associated genes in cervical cancers resected in the proliferative and secretory phases of the menstrual cycle

Previous retrospective studies suggest that the phase of the menstrual cycl e at surgery (proliferative versus secretory) for breast cancer may signifi cantly affect patient survival. Fluctuations during the menstrual cycle of the expression of genes involved in metastases in breast cancer tissue have also been reported. We hypothesized that the menstrual phase may also affe ct similar changes in gene expression of other cancers. We focused our atte ntion on cancer of the uterine cervix because the hysterectomy specimen obt ained at original surgery for the cancer can be used retrospectively to det ermine cycle phase. We analyzed tumor specimens from 36 premenopausal cervi cal cancer patients who had undergone hysterectomy as their primary treatme nt, We used reverse transcription-PCR to quantify gene expression during th e different phases of the menstrual cycle as determined from the endometria l specimen. We explored a panel of genes that may affect metastatic propens ity, namely, metalloproteinase-9 (MMP-9), tissue inhibitor of metalloprotei nase-2 (TIMP-2), cyclooxygenase 1 and 2 (COX-1 and COX-2), and vascular end othelial growth factor (VEGF). A significantly higher level of TIMP-2 and C OX-2 gene expression (P = 0.007 and 0.030, respectively) was detected durin g the proliferative phase compared to the secretory phase of the cycle. The expression of the other genes was not significantly affected by the stage of the menstrual cycle. The finding that TIMP-2 and COX-2 expression in cer vical cancer may be affected by the stage of the menstrual cycle supports t he hypothesis that ovarian hormones may affect the expression of genes invo lved in metastasis, These findings need to he replicated, and their implica tions for tumor angiogenesis, invasion, and metastatic propensity need to b e explored both in human studies and in experimental models.