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

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

REIKO DEHARI,¹ YOSHIYASU NAKAMURA,² NAOYUKI OKAMOTO³ and HIROKI NAKAYAMA⁴

¹Department of Surgical Pathology, Kanagawa Cancer Center Hospital, Kanagawa, Japan
²Division of Molecular Pathology & Genetics, Kanagawa Cancer Center Research Institute, Kanagawa, Japan
³Division of Cancer Prevention & Cancer Control, Kanagawa Cancer Center Research Institute, Kanagawa, Japan
⁴Department of Gynecology, Kanagawa Cancer Center Hospital, Kanagawa, Japan

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.

keywords —— Uterine cervical neoplasm; Young patient; Poor prognosis; Nuclear-localized growth hormone receptor; human papilloma virus.

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Tohoku J. Exp. Med., 2008, 216, 165-172

Correspondence: Reiko Dehari, Department of Surgical Pathology, Kanagawa Cancer Center Hospital, 1-1-2, Nakao, Asahi-ku, Yokohama, 241-0815, Japan.

e-mail: rdehari@hotmail.com