Anti-Helicobacter pylori antibodies in cervical mucus: a new cause of infertility

Objective

The aims of our study were to determine on the one hand a correlation between the presence of anti-Helicobacter pylori (anti-H. pylori) IgG antibodies in serum and cervical mucus of women with idiopathic infertility, and on the other hand the effect of these antibodies on cervical mucus quality, in particular related to the ability of spermatozoa to penetrate it.

Study design

We analysed anti-H. pylori IgG antibodies in the serum and cervical mucus of 67 patients diagnosed with idiopathic infertility using the Quanta Lite H. pylori IgG test. The penetration of normal sperm, in 15 cervical mucus samples positive for anti-H. pylori antibodies and in 15 negative samples, was assessed using the simplified slide test.

Results

A significant positive correlation emerged between anti-H. pylori IgG antibody concentrations in the serum and in the cervical mucus (r = 0.9275; p < 0.00001). In the 15 anti-H. pylori IgG mucus-positive samples the slide test showed abnormal penetration by the spermatozoa.

Conclusions

Our study demonstrated that the presence of anti-H. pylori antibody in the cervical mucus can be involved in female infertility, interfering with sperm progression. Considering the close correlation found between serum and cervical mucus anti-H. pylori antibody titres, measuring serum antibodies could become an additional test, in particular in couples with unexplained infertility.     

Characterization of mast cells according to their content of tryptase and chymase in normal and neoplastic human uterine cervix

Abstract. Cabanillas-Saez A, Schalper JA, Nicovani SM, Rudolph MI. Characterization of mast cells according to their content of tryptase and chymase in normal and neoplastic human uterine cervix.
Mast cells (MC) have been associated with diverse human cancers. The primary function of these cells is to store and release a number of biologically active mediators, including the serine proteases tryptase and chymase. These proteases have been closely related with angiogenesis and tumor invasion, two critical steps during tumor progression. In the present work we analyzed the presence of MC in human uterine cervix from both normal and neoplastic tissues by using metachromatic, immunohistochemical, and enzymohistochemical staining. Tryptase-positive (MC_T)– and tryptase/chymase-positive (MC_TC)–mast cells were found in both normal and neoplastic tissues. The phenotype predominantly expressed in normal tissues as well as in benign and malignant lesions of the uterine cervix was the MC_T. The total number of MC remained constant through the different stages of malignant transformation (cervical intraepithelial neoplasia grade 1–3) but a significant increase in the invasive carcinoma (IC) group was observed, this increase being mainly due to the MC_T phenotype. Furthermore, we detected abundant MC_T but not MC_TC infiltrating tumors in sections of IC. Regarding the potent angiogenic properties described for tryptase, these findings suggest that in advanced stages of malignancy the significant number of MC_T distributed within the cervical tissues could provide an effective mechanism to create the abundantly vascularized microenvironment required for tumor cells to proliferate and disseminate.     

Cancerous inhibitor of protein phosphatase 2A is overexpressed in cervical cancer and upregulated by human papillomavirus 16 E7 oncoprotein

Objectives

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein stabilizing c-Myc and promoting cell proliferation and transformation. Here we investigated the role of CIP2A in cervical cancer in vivo and in vitro.

Methods

CIP2A expression was assessed in normal cervical, cervical intraepithelial neoplasia (CIN) I to III and cervical cancer tissues by immunohistochemistry and RT-PCR. Cell growth was explored by cell proliferation assay, colony formation assay and anchorage-independent growth in soft agar after inhibition of CIP2A by siRNA in HeLa, SiHa and Caski cells. Crosstalk of CIP2A and HPV16 E7 was investigated by immunohistochemistry in cervical cancer tissues and by real-time PCR and western blot analysis after HPV16 E7 inhibition by siRNA in SiHa cells.

Results

CIP2A was transcribed in 73.3% of cervical cancer tissues (n = 15) but not in normal cervical tissues (n = 8). CIP2A protein was detected in 52.8% of cervical cancer (n = 72) and 12.5% of CIN III tissues (n = 24) but not in normal (n = 15), CIN I (n = 21) or CIN II samples (n = 25). CIP2A protein level was positively associated with HPV16 E7 level in cervical cancer tissues. CIP2A expression was markedly reduced after E7 depletion. Moreover, CIP2A depletion reduced c-Myc protein level and impaired proliferation and growth of cervical cancer cells.

Conclusions

CIP2A is overexpressed in cervical cancer and promotes the malignant growth of cervical cancer cells. Its expression is upregulated by HPV16 E7. Therefore, CIP2A plays an important role in carcinogenisis of cervical cancer and shows promise for the diagnosis and treatment of cervical cancer.