Increased Nuclear Expression of Growth Hormone Receptor in Uterine Cervical Neoplasms of Women under 40 Years Old

Abstract

There has been an increased incidence of cervical cancer among young women, and they tend to have a poor prognosis due to unknown reasons. We hypothesize growth hormone (GH) receptor (GHR) may be involved in the proliferation of cervical carcinoma, because GH-related neoplasms arise in various organs and the amount of GH secretion may be different according to age. GHR is normally expressed in the cell membrane and cytoplasm, while the nuclear distribution of GHR has been considered to reflect high proliferative activity of cells. We analyzed the subcellular localization of GHR by immunohistochemistry in cervical neoplasms of 55 patients (38.6 ± 13.9 years old): 33 patients (< 40 years) and 22 patients (≥ 40 years). Nuclear expression of GHR was detected in more than 50% of neoplastic cells present in the tissue samples derived from 20 patients under 40 years (20/33, 61%), whereas less than 25% of neoplastic cells expressed GHR in their nuclei in 17 patients over 40 years (17/22, 77%). In contrast, more than 75% of neoplastic cells showed cytoplasmic GHR expression in the tissues derived from both age groups. Furthermore, the population of cells with nuclear GHR expression was high in the squamous epithelium and the stromal cells of patients under 40, but low in patients over 40. The GH-GHR signal may act at the nuclear level to promote the proliferation of uterine cervical neoplasms in young patients. We suggest the involvement of GHR in progression of uterine cervical carcinoma.Uterine cervical neoplasm; Young patient; Poor prognosis; Nuclear-localized growth hormone receptor; human papilloma virus. Human papilloma virus (HPV) infection is associated with the carcinogenesis of cervical carcinoma. Recently, in Japan, there has been an increased incidence of cervical cancer among young women. It seems that recent changes in sexual behavior such as a decrease in age of first intercourse and an increase in the number of sexual partners has resulted in the spread of HPV infection among young women and led to an increase in the morbidity rate for cervical cancer

Role of the growth hormone–IGF-1 axis in cancer

“…Tissue immunohistochemistry reveals that the nuclear GHR is present in many proliferating cells, including a variety of cancers, such as breast cancer [92], colorectal carcinoma [93], hepatocellular carcinoma [94], melanoma [70] and uterine cervical neoplasms [95]. The translocation of a transmembrane receptor into the nucleus is known to occur for the EGFR, the FGF receptor and IFN-g receptor [96], and is often associated with cell transformation.…”

Extrapituitary growth hormone

“…Indeed, the progression of uterine cervical carcinoma in women has also been correlated with the appearance of the GHR in the nucleus of cancerous cells [279], and nuclear GHR expression is similarly a marker of tumorigenesis in other cancerous cells [241,280]. Nuclear targeting of the GH receptor is thought to induce cell proliferation, a dysregulated proliferative arrest and an induction of cell cycle progression, through increased expression of the proliferation-related proteins Survivin and Mybbp [280].…”

Growth factors as treatment for inflammatory bowel disease: A concise review of the evidence toward their potential clinical utility

“…[9] GH have shown a potential carcinogenic role in colorectal cancer,[10] primary Ki-1 lymphoma of the skin,[11] liposarcoma and lipoma,[12] hepatocarcinoma,[13] breast cancer,[14] prostate cancer[15] and uterine cervical cancer. [16] The trials regarding the usefulness of GH in IBD have not reported an increased incidence of cancer.…”