Profiling estrogen, progesterone, and androgen receptors in colorectal cancer in relation to gender, menopausal status, clinical stage, and tumour sidedness

BackgroundAlthough estrogen (ERα/ERβ), progesterone (PGR), and androgen (AR) receptors are pathologically altered in colorectal cancer (CRC), their simultaneous expression within the same cohort of patients was not previously measured.MethodsERα/ERβ/PGR/AR proteins were measured in archived paired normal and malignant colon specimens (n =120 patients) by immunohistochemistry, and results were analyzed by gender, age (≤50 vs. ≥60 years), clinical stages (early-stage I/II vs. late-stage III/IV), and anatomical location (right; RSCs vs. left; LSCs). Effects of 17β-estradiol (E2), progesterone (P4), and testosterone alone or combined with the specific blockers of ERα (MPP dihydrochloride), ERβ (PHTPP), PGR (mifepristone), and AR (bicalutamide) on cell cycle and apoptosis were also measured in the SW480 male and HT29 female CRC cell lines. ResultsERα and AR proteins increased, whilst ERβ and PGR declined markedly in malignant specimens. Moreover, male neoplastic tissues showed highest AR expression, whilst ERβ and PGR weakest alongside ERα strongest expression was seen in cancerous tissues from women aged ≥60 years. Late-stage neoplasms also revealed maximal alterations in the expression of sex steroid receptors. By tumor location, LSCs disclosed significant elevations in ERα with marked declines in PGR compared with RSCs, and ERα strongest alongside PGR weakest expression was detected in advanced LSCs from women aged ≥60 years. Late-stage LSCs from females aged ≥60 years also showed weakest ERβ and strongest AR expression. In contrast, male RSC and LSC tissues exhibited equal ERβ and AR expression in all clinical stages. ERα and AR proteins also correlated positively, whereas ERβ and PGR inversely, with tumor characteristics. Concomitantly, E2 and P4 monotherapies triggered cell cycle arrest and apoptosis in the SW480 and HT29 cells, and while pre-treatment with ERα-blocker enhanced the effects of E2, ERβ-blocker and PGR-blocker suppressed the E2 and P4 anti-cancer actions, respectively. In contrast, treatment with the AR-blocker induced apoptosis, whilst co-treatment with testosterone hindered the effects. ConclusionsThis study advocates that protein expression of sex steroid receptors in malignant tissues could represent prognostic markers, as well as hormonal therapy could provide an alternative strategy against CRC, and their efficacies could be dependent on gender, clinical stage, and tumor location

Reed's Syndrome: A Case of Multiple Cutaneous Leiomyomas Treated with Liquid Nitrogen Cryotherapy

Reed's syndrome is an autosomal dominant genetic disorder. Affected individuals are at increased risk of developing benign smooth muscle tumors in the skin and uterus. In this article, we report a case of a 52-year-old female who presented to our dermatology clinic complaining of painful skin lesions on her right arm, left forearm and trunk. The patient had a past medical history of uterine leiomyomatosis for which she underwent hysterectomy 17 years ago. The patient's family history revealed that her mother, 2 sisters and 2 maternal aunts also had uterine leiomyomas. The diagnosis of Reed's syndrome was confirmed by histopathologic examination of the patient's dermal lesion in conjunction with her surgical and family histories. Five years after the initial presentation, the patient underwent treatment with liquid nitrogen cryotherapy for the dermal leiomyomas. After the treatment, marked improvement was noticed with regard to the pain and size of the skin lesions