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

Bauernhofer T, Pichler M, Wieckowski E, Stanson J, Aigelsreiter A, Griesbacher A, Groselj-Strele A, Linecker A, Samonigg H, Langner C, Whiteside TL - Br. J. Cancer (2011)

Bottom Line: Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs).The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome.Our data indicate that hPRL is an important growth factor for SCCHN.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz A-8036, Austria. thomas.bauernhofer@medunigraz.at

ABSTRACT

Background: The influence of human prolactin (hPRL) on the development of breast and other types of cancer is well established. Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs).

Methods: In this study, we evaluated prolactin receptor (PRLR) expression in SCCHN cell lines and assessed by immunohistochemistry the expression in 89 patients with SCCHNs. The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome. The effect of hPRL treatment on tumour cell growth was evaluated in vitro.

Results: Immunoreactivity for PRLR was observed in 85 out of 89 (95%) tumours. Multivariate COX regression analysis confirmed high levels of PRLR expression (>25% of tumour cells) to be an independent prognostic factor with respect to overall survival (HR=3.70, 95% CI: 1.14-12.01; P=0.029) and disease-free survival (P=0.017). Growth of PRLR-positive cancer cells increased in response to hPRL treatment.

Conclusion: Our data indicate that hPRL is an important growth factor for SCCHN. Because of PRLR expression in a vast majority of tumour specimens and its negative impact on overall survival, the receptor represents a novel prognosticator and a promising drug target for patients with SCCHNs.

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Kaplan–Meier plots for overall survival (A) and disease-free survival (B) in patients with SCCHNs with low vs high PRLR expression.
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fig4: Kaplan–Meier plots for overall survival (A) and disease-free survival (B) in patients with SCCHNs with low vs high PRLR expression.

Mentions: To evaluate whether PRLR expression is associated with the outcome of patients with SCCHN, we determined PRLR expression by immunohistochemistry in a larger set of human SCCHN tumour samples. Expression of PRLR was observed in 89 primary tumours with 8 (9%) cases showing focal, 16 (18%) moderate and 65 (73%) extensive immunoreactivity, respectively (Figure 3). Median follow-up was 70 months (mean 73, range 1–202). The 5-year disease-free survival was observed in 43 (48%) patients, 46 (52%) patients developed disease recurrence including 6 (7%) patients who developed distant metastasis and 41 (46%) died during a 5-year follow-up period. A comparison of the moderate PRLR expression group (25–75%) with the extensive PRLR expression group (>75%) showed no differences for clinical outcome in the univariate analysis. Therefore, we compared focal expression (<25%) (categorised to the PRLR low expression group) vs moderate and/or extensive expression (categorised to the PRLR high expression group) and found that a higher degree of PRLR expression was associated with decreased disease-free and overall survival. After a cutoff value of 25% positive tumour cells had been identified as the strongest discriminator for patient outcome, all subsequent analyses used this value, and we defined tumours showing <25% PRLR-positive tumour cells as the PRLR low expression group and tumours showing >25% PRLR-positive tumour cells as the PRLR high expression group. Over the complete follow-up period, the rate of disease recurrence (75 vs 38%, P<0.05), including distant metastases (7 vs 0%), was higher in the PRLR high expression group compared with the PRLR low expression group. Also, 58 out of 81 (72%) patients with tumours with high PRLR expression and 3 out of 8 (38%) patients with tumours showing low PRLR expression died during the follow-up period (P=0.023, log-rank test; Figure 4A). Disease-free survival after 5 years was documented in 36 out of 81 (44%) patients with tumours with high PRLR expression and 7 out of 8 (87%) patients with tumours showing low PRLR expression (P=0.017, log-rank test, Figure 4B). Furthermore, T and N classification, both known to define a poor prognosis in SCCHNs, were significantly associated with disease-free and overall survival (data not shown). No association between PRLR expression and clinicopathological parameters, such as T and N classification as well as tumour differentiation, gender and age, was observed (Table 4). To determine the independent prognostic value of PRLR expression on patients' outcome, a multivariate analysis using a Cox proportional hazard model was performed. In Cox's proportional hazards regression models including PRLR expression, T and N classification, tumour grade, as well as patient age and gender, we identified advanced tumour stages (stage I and II vs III and IV; HR=1.78, 95% CI: 1.03–3.05; P=0.034), nodal positive disease (nodal negative vs nodal positive disease; HR=2.20, 95% CI: 1.30–3.75; P=0.003) and high PRLR immunoreactivity (low vs high expression group; HR=3.70, 95% CI: 1.14–12.01; P=0.029) as independent prognostic variables with respect to overall survival. For the other parameters tested, no independent influence on outcome was observed.


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

Bauernhofer T, Pichler M, Wieckowski E, Stanson J, Aigelsreiter A, Griesbacher A, Groselj-Strele A, Linecker A, Samonigg H, Langner C, Whiteside TL - Br. J. Cancer (2011)

Kaplan–Meier plots for overall survival (A) and disease-free survival (B) in patients with SCCHNs with low vs high PRLR expression.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101909&req=5

fig4: Kaplan–Meier plots for overall survival (A) and disease-free survival (B) in patients with SCCHNs with low vs high PRLR expression.
Mentions: To evaluate whether PRLR expression is associated with the outcome of patients with SCCHN, we determined PRLR expression by immunohistochemistry in a larger set of human SCCHN tumour samples. Expression of PRLR was observed in 89 primary tumours with 8 (9%) cases showing focal, 16 (18%) moderate and 65 (73%) extensive immunoreactivity, respectively (Figure 3). Median follow-up was 70 months (mean 73, range 1–202). The 5-year disease-free survival was observed in 43 (48%) patients, 46 (52%) patients developed disease recurrence including 6 (7%) patients who developed distant metastasis and 41 (46%) died during a 5-year follow-up period. A comparison of the moderate PRLR expression group (25–75%) with the extensive PRLR expression group (>75%) showed no differences for clinical outcome in the univariate analysis. Therefore, we compared focal expression (<25%) (categorised to the PRLR low expression group) vs moderate and/or extensive expression (categorised to the PRLR high expression group) and found that a higher degree of PRLR expression was associated with decreased disease-free and overall survival. After a cutoff value of 25% positive tumour cells had been identified as the strongest discriminator for patient outcome, all subsequent analyses used this value, and we defined tumours showing <25% PRLR-positive tumour cells as the PRLR low expression group and tumours showing >25% PRLR-positive tumour cells as the PRLR high expression group. Over the complete follow-up period, the rate of disease recurrence (75 vs 38%, P<0.05), including distant metastases (7 vs 0%), was higher in the PRLR high expression group compared with the PRLR low expression group. Also, 58 out of 81 (72%) patients with tumours with high PRLR expression and 3 out of 8 (38%) patients with tumours showing low PRLR expression died during the follow-up period (P=0.023, log-rank test; Figure 4A). Disease-free survival after 5 years was documented in 36 out of 81 (44%) patients with tumours with high PRLR expression and 7 out of 8 (87%) patients with tumours showing low PRLR expression (P=0.017, log-rank test, Figure 4B). Furthermore, T and N classification, both known to define a poor prognosis in SCCHNs, were significantly associated with disease-free and overall survival (data not shown). No association between PRLR expression and clinicopathological parameters, such as T and N classification as well as tumour differentiation, gender and age, was observed (Table 4). To determine the independent prognostic value of PRLR expression on patients' outcome, a multivariate analysis using a Cox proportional hazard model was performed. In Cox's proportional hazards regression models including PRLR expression, T and N classification, tumour grade, as well as patient age and gender, we identified advanced tumour stages (stage I and II vs III and IV; HR=1.78, 95% CI: 1.03–3.05; P=0.034), nodal positive disease (nodal negative vs nodal positive disease; HR=2.20, 95% CI: 1.30–3.75; P=0.003) and high PRLR immunoreactivity (low vs high expression group; HR=3.70, 95% CI: 1.14–12.01; P=0.029) as independent prognostic variables with respect to overall survival. For the other parameters tested, no independent influence on outcome was observed.

Bottom Line: Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs).The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome.Our data indicate that hPRL is an important growth factor for SCCHN.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz A-8036, Austria. thomas.bauernhofer@medunigraz.at

ABSTRACT

Background: The influence of human prolactin (hPRL) on the development of breast and other types of cancer is well established. Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs).

Methods: In this study, we evaluated prolactin receptor (PRLR) expression in SCCHN cell lines and assessed by immunohistochemistry the expression in 89 patients with SCCHNs. The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome. The effect of hPRL treatment on tumour cell growth was evaluated in vitro.

Results: Immunoreactivity for PRLR was observed in 85 out of 89 (95%) tumours. Multivariate COX regression analysis confirmed high levels of PRLR expression (>25% of tumour cells) to be an independent prognostic factor with respect to overall survival (HR=3.70, 95% CI: 1.14-12.01; P=0.029) and disease-free survival (P=0.017). Growth of PRLR-positive cancer cells increased in response to hPRL treatment.

Conclusion: Our data indicate that hPRL is an important growth factor for SCCHN. Because of PRLR expression in a vast majority of tumour specimens and its negative impact on overall survival, the receptor represents a novel prognosticator and a promising drug target for patients with SCCHNs.

Show MeSH
Related in: MedlinePlus