Justin C. Konje

Expression, Distribution and Function of the Transient Receptor Potential Vanilloid Type 1 (TRPV1) in Endometrial Cancer

The transient receptor potential vanilloid 1 receptor (TRPV1) is a calcium-sensitive membrane receptor activated by capsaicin and the endocannabinoid, anandamide (AEA). Once activated in vitro, endometrial cancer (EC) cell growth appears to be inhibited through increased apoptosis, but the mechanism remains unclear. Our aim was to investigate the expression and distribution of TRPV1 in normal and cancerous endometria and to determine the precise in vitro mechanism of decreased EC cellular growth. TRPV1 expression in patients with endometrial carcinoma (15 Type 1 EC, six Type 2 EC) and six normal patients (atrophic endometria) was assessed using quantitative RT-PCR and immunohistochemistry (IHC). Additionally, immunohistochemical staining for the proliferation marker Ki-67, the pro-apoptotic marker BAX and the anti-apoptotic marker Bcl-2 were explored. TRPV1 transcript (p = 0.0054) and immunoreactive protein (p < 0.0001) levels were significantly reduced in all EC tissues when compared to control (atrophic) endometria. The almost 50% reduction in TRPV1 transcript levels was mirrored by an almost complete loss of immunoreactive TRPV1 protein. The increased proliferation (Ki-67) of EC tissues correlated with the expression of mutated BAX and inversely correlated to Bcl-2, but only in Type 2 EC samples. In vitro, AEA caused a decrease in Ishikawa cell numbers, whilst capsaicin did not, suggesting the anti-proliferative effect of AEA in EC cells is not via the TRPV1 receptor. In conclusion, the loss of TRPV1 expression in vivo plays a role in the aetiopathogenesis of EC. Activation of cells by AEA also probably promotes EC cell loss through a pro-apoptotic mechanism not involving TRPV1.

Expression of the putative cannabinoid receptor GPR55 is increased in endometrial carcinoma

AbstractAlthough the expression of the putative cannabinoid receptor GPR55 has been shown to be involved in the growth of various tumours and is increased in a number of cancers, its expression has not been examined in patients with endometrial cancer (EC). Quantitative RT-PCR (for mRNA levels) and immunohistochemistry (for protein levels) were used to measure GPR55 expression in patients with Type 1 and Type 2 EC and correlated against cannabinoid receptor (CB1 and CB2) protein levels using non-cancerous endometrium as the control tissue. The data indicated that GPR55 transcript and GPR55 protein levels were significantly (p < 0.002 and p < 0.0001, respectively) higher in EC tissues than in control tissues. The levels of immunoreactive GPR55 protein were correlated with GPR55 transcript levels, but not with the expression of CB1 receptor protein, and were inversely correlated with CB2 protein expression, which was significantly decreased. It can be concluded that GPR55 expression is elevated in women with EC, and thus could provide a potential novel biomarker and therapeutic target for this disease.

Human papillomavirus (HPV) in pregnancy – An update

Human papilloma viruses (HPV) are small epitheliotropic DNA viruses, of which there are 200 genotypes, 40 of which are known to cause genital infections and are also oncogenic. HPV is the most common sexually transmitted infection. Clinical features vary from asymptomatic (identified at routine cervical cancer screening) to large lesions on the vulva, vagina, cervix and some extragenital sites. Its prevalence in pregnancy varies from 5.5% to 65% depending on age, geography and gestational age (increasing with gestational age). Infection in pregnancy has been associated with adverse outcomes such as spontaneous miscarriage, preterm birth, placental abnormalities and fetal growth restriction. However, the evidence for these adverse outcomes is varied. Besides being oncogenic (and thus associated with cancer of the cervix in pregnancy), vertical transmission to the fetus/neonate can cause neonatal infections, especially juvenile-onset recurrent oral and respiratory papillomatosis (JORRP). Where there are very large lesions on the vulva, delivery may be obstructed. Diagnosis in pregnancy is mainly by viral PCR or from the clinical appearance of the characteristic lesions on the vulva. Treatment is local by either surgical or laser excision or application of trichloroacetic acid. Podophyllin/podophyllotoxin is contraindicated in pregnancy. HPV Infection is not an indication for caesarean delivery as this has not been shown to prevent vertical transmission. For those diagnosed at routine cervical cancer screening, management should follow guidelines for cervical cancer screening in pregnancy. Vaccination is currently not recommended for pregnant women, although studies on those inadvertently vaccinated in pregnancy have not shown any adverse effects on either the fetus or mother.