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Expression of folate receptors and heterogeneous nuclear ribonucleoprotein E1 in women with human papillomavirus mediated transformation of cervical tissue to cancer

¹ Department of Laboratory Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala State, India
² Gynecological Oncology Specialty Clinic, Regional Cancer Centre, Thiruvananthapuram
³ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, and the Richard L Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA
⁴ Division of Hematology-Oncology, Department of Medicine, Indiana University School of Medicine, and the Richard L Roudebush Veterans Affairs Medical Center

Correspondence to:
Professor M R Pillai, Department of Laboratory Medicine, Regional Cancer Centre, Thiruvananthapurom, Kerala State, India;
mrpillai{at}vsnl.com or Professor A C Antony, Indiana Cancer Research Institute, 1044 West Walnut Street, R4–266, Indianapolis, IN 46202, USA;
aantony{at}iupui.edu Aims: Folate receptors (FRs) mediate cellular uptake of folates in many cancer cells and in folate deficiency heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) mediates translational upregulation of FR in cultured cervical cancer cells. hnRNP-E1 can also interfere with human papillomavirus 16 (HPV-16) viral capsid protein synthesis (and thereby HPV proliferation) in vitro. This study aimed to evaluate prospectively the relevance of FR and hnRNP-E1 expression in the normal cervix, cervical dysplasia, and cancer.

Methods: Cervical tissues from 12 women with normal histology and 69 consecutive women with varying grades of cervical dysplasia and cancer were prospectively evaluated for immunohistochemical expression of FR, hnRNP-E1, proliferating cell nuclear antigen (PCNA), and HPV. There were 22 women with low grade squamous intraepithelial lesions (LGSIL), 22 with high grade squamous intraepithelial lesions (HGSIL), and 25 with invasive cervical carcinoma.

Results: Among normal subjects, 100% and 92% expressed hnRNP-E1 and FR, respectively. FR expression decreased from 91% in LGSIL to 68% and 64% in women with HGSIL and cancer, respectively. Similarly, hnRNP-E1 expression decreased from 86% in LGSIL to 68% and 40% in HGSIL and cancer, respectively. There was a highly significant positive correlation between the extent of FR and hnRNP-E1 expression, and an inverse correlation between HPV infection and hnRNP-E1 expression during progression of cervical dysplasia to cancer.

Conclusion: These results are consistent with a hypothesis that reduced hnRNP-E1 expression may be permissive for HPV proliferation and progression to cervical cancer, and support the need for prospective longitudinal studies of hnRNP-E1 expression in HPV-16 infected women.

Keywords: folate receptors; heterogenous nuclear ribonucleoprotein E1; cervical cancer; human papillomavirus

Abbreviations: FR, folate receptors; hnRNP-E1, heterogenous nuclear ribonucleoprotein E1; LGSIL, low grade squamous intraepithelial lesion; HGSIL, high grade squamous intraepithelial lesion; PCNA, proliferating nuclear antigen; PCR, polymerase chain reaction

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