Prolactin as a local growth promoter in patients with locally advanced tongue cancer: GCRI experience

Abstract

Background The purpose of this study was to assess the role of prolactin (PRL) in men with locally advanced tongue cancer. Methods Circulating PRL was assayed immunoradiometrically in pretherapeutic and sequential blood samples of 99 patients with locally advanced tongue cancer. Patients were followed for 3 years or until their death within a stipulated time. Immunohistochemical localization of PRL was performed on formalin‐fixed paraffin‐embedded tissue sections. Tumoral prolactin receptors (PRLR) were estimated by ligand binding assay; the expression of PRL mRNA and PRLR mRNA were carried out by reverse transcriptase polymerase chain reaction (RT‐PCR). Furthermore, PRL amplimer was sequenced and compared with human pituitary PRL amplimer. Results Pretherapeutic PRL levels were significantly higher in patients with locally advanced tongue cancer compared with controls (p = .01). Thirty‐four percent (34 of 99) of the patients had hyperprolactinemia (PRL ≥15.0 ng/mL). Univariate survival analysis showed that patients with pretherapeutic hyperprolactinemia had a significantly shorter overall survival than patients with pretherapeutic PRL <15.0 ng/mL serum (p = .0009). In multivariate analysis, PRL emerged as the most significant independent prognostic factor influencing overall survival. Furthermore, changes in serial PRL levels showed excellent correlation with response to therapy and progression of disease. Forty‐four percent (24 of 54) of the tumors showed positive immunoreactivity with PRL antibody, indicating that PRL or a molecule similar to it is produced by tongue tumors. PRL mRNA expression was seen in 85% (43 of 50) of the tumors and confirmed the de novo synthesis of PRL. Sequence analysis of the 234 bp PRL amplimer revealed that the sequence was homologous to exon 5 of pituitary PRL mRNA. The action of PRL is mediated by PRLR, and it was observed that the PRLR positivity by ligand binding assay was 33%. The expression of PRLR mRNA by RT‐PCR showed two forms of PRLR mRNA (ie, intermediate form [500–600 bp] seen in 82% (41 of 50 ) of the tumors and the long form [800–900 bp] seen in 36% (18 of 50) of the tumors. In 82% (41 of 50) of the tumors, either the intermediate or long form was seen. Conclusions This multifaceted study of PRL suggests that tongue cancer cells produce PRL, and this ectopically produced PRL might be acting as a major local growth promoter by means of autocrine and paracrine mechanisms. Looking at its prognostic value and correlation with disease activity, it may provide new insights into treatment of tongue cancer. © 2000 John Wiley & Sons, Inc. Head Neck 22: 257–264, 2000.

A review of the most promising biomarkers for early diagnosis and prognosis prediction of tongue squamous cell carcinoma

“…In thirteen studies, the potential of salivary and blood biomarkers in tongue cancer was evaluated (Table 1). Five of these papers assessed the performance of 14 different markers for early diagnosis, 19–23 seven assessed performance for prognosis, 24–30 while the final study, dealing on pro-inflammatory cytokines, assessed both diagnostic and prognostic performance. 31 Within the included studies, the most promising biomarkers were IL-6 and IL-8 that showed consistent evidence for clinical usefulness in detection and diagnosis, and prolactin in prognosis.…”

Prolactin receptor is a negative prognostic factor in patients with squamous cell carcinoma of the head and neck

“…The molecular mechanisms underlying this result have yet to be clarified. Bhatavdekar et al (2000) detected hPRL protein and mRNA expression in 44 and 85% of SCCHN patients, respectively, and proposed a role for hPRL as a local growth promoter. However, there is currently no study available that investigates the influence of hPRL on the growth of SCCHN cancer cells generated from primary tumours and their corresponding metastases.…”

“…In the second study, PRLR measured by a ligand binding assay and by PRLR mRNA using RT–PCR were detectable in 8 out of 24 (33%) and 41 out of 50 (82%) of tumour samples, respectively. However, follow-up data, including clinical outcome, were not available in that investigation (Bhatavdekar et al , 2000). Our study shows for the first time that in a large cohort of patients, PRLR expression in tumour tissues is significantly associated with a decreased survival in SCCHN patients.…”

“…In this study, hyperprolactinemia proved to be an independent predictor of short-term prognosis in tongue cancer patients. In a larger trial conducted by the same group, hPRL serum levels in patients with advanced tongue cancer were significantly higher compared with control subjects, and hPRL serum levels were identified as an independent prognostic factor for overall patient survival (Bhatavdekar et al , 2000). In contrast to these data, Meyer et al (2010) recently reported that circulating serum hPRL levels did not significantly predict outcome in a study of 527 patients with SCCHNs.…”

Domperidone use and risk of primary liver cancer in the Clinical Practice Research Datalink

“…In specific, there was an increased risk of upper and lower gastrointestinal cancer, with a higher risk among women than men. Other studies have reported higher prolactin levels among persons with several cancer types [36][37][38][39][40], including hepatocellular carcinoma, the dominant histological type of liver cancer [41][42][43][44]. In these cross-sectional studies, serum prolactin levels, or protein expression of prolactin in tissue samples, were significantly higher in hepatocellular carcinoma cases than in controls [41][42][43][44].…”