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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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PRLR expression in SCCHN cell lines. (A) PRLR expression measured by flow cytometry in PCI-6A, PCI-6B and T47D cell lines. The PCI-6A cell line shows a significantly higher percentage of PRLR+ cells compared with the PCI-6B cell line. (B) Immunocytochemical staining of SCCHN cell lines (magnification × 400). Positive membranous and cytoplasmic PRLR staining (red colour of Cy3) is shown for the PCI-6A cell line, whereas the PCI-6B cell line is negative. Nuclei are counterstained with Hoechst dye (blue). (C) Immunoprecipitation reveals a prominent band between 75 and 80 kD, corresponding to the PRLR protein in the lysate of PCI-6A cells, whereas only a weak band was detected in the lysate of PCI-6B cells. Immunoglobulin G (IgG) heavy chain was used as a loading control and T47D cell line served as a positive control.
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fig1: PRLR expression in SCCHN cell lines. (A) PRLR expression measured by flow cytometry in PCI-6A, PCI-6B and T47D cell lines. The PCI-6A cell line shows a significantly higher percentage of PRLR+ cells compared with the PCI-6B cell line. (B) Immunocytochemical staining of SCCHN cell lines (magnification × 400). Positive membranous and cytoplasmic PRLR staining (red colour of Cy3) is shown for the PCI-6A cell line, whereas the PCI-6B cell line is negative. Nuclei are counterstained with Hoechst dye (blue). (C) Immunoprecipitation reveals a prominent band between 75 and 80 kD, corresponding to the PRLR protein in the lysate of PCI-6A cells, whereas only a weak band was detected in the lysate of PCI-6B cells. Immunoglobulin G (IgG) heavy chain was used as a loading control and T47D cell line served as a positive control.

Mentions: The PRLR expression was initially assessed in SCCHN cell lines (n=8) established from primary tumours and the corresponding metastases from four patients. The breast cancer cell line T47D served as the positive control. The PRLR expression was determined in the SCCHN lines by flow cytometry and immunocytochemistry. Of the eight SCCHN lines, five (4A, 4B, 6A, 37A, 37B) were positive for PRLR expression (Table 3). The only pair of SCCHN cell lines with a heterogeneous PRLR expression profile was PCI-6A and PCI-6B (Figure 1A). The majority of PCI-6A cells, which had been generated from a primary tumour, were highly PRLR positive, whereas all PCI-6B cells generated from a metachronously developed corresponding lymph node metastasis were negative for PRLR, both on the cell surface and in the cytoplasm (Figure 1B). To substantiate the specificity of PRLR staining results, we examined PRLR expression in the SCCHN cell lines PCI-6A and PCI-6B using immunoprecipitation. In accordance with data obtained from immunocytochemistry and flow cytometry, PRLR immunoprecipitation resulted in a prominent band at 80 kDa that corresponded to the PRLR-predicted molecular weight using lysate from PCI-6A cells, whereas only a weak band was detected in PCI-6B cell lysate (Figure 1C). To exclude the possibility that the divergent PRLR expression profiles of PCI-6A and PCI-6B cells might be because of culture selection, we evaluated PRLR expression in sections of the primary tumour and the metachronously developed lymph node metastasis by immunohistochemistry (Figure 2). The results from these samples confirmed the data obtained from the cell lines. To further validate the results obtained with the SCCHN lines, we examined 13 tissue specimens of primary and metastatic SCCHNs randomly selected from the institutional tumour tissue archive. Breast tissue specimens known to express PRLR served as control. Of 13 SCCHN specimens, 9 (69%) were positive for PRLR expression based on the intensity of PRLR staining and the distribution of positive cells (data not shown).


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)

PRLR expression in SCCHN cell lines. (A) PRLR expression measured by flow cytometry in PCI-6A, PCI-6B and T47D cell lines. The PCI-6A cell line shows a significantly higher percentage of PRLR+ cells compared with the PCI-6B cell line. (B) Immunocytochemical staining of SCCHN cell lines (magnification × 400). Positive membranous and cytoplasmic PRLR staining (red colour of Cy3) is shown for the PCI-6A cell line, whereas the PCI-6B cell line is negative. Nuclei are counterstained with Hoechst dye (blue). (C) Immunoprecipitation reveals a prominent band between 75 and 80 kD, corresponding to the PRLR protein in the lysate of PCI-6A cells, whereas only a weak band was detected in the lysate of PCI-6B cells. Immunoglobulin G (IgG) heavy chain was used as a loading control and T47D cell line served as a positive control.
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fig1: PRLR expression in SCCHN cell lines. (A) PRLR expression measured by flow cytometry in PCI-6A, PCI-6B and T47D cell lines. The PCI-6A cell line shows a significantly higher percentage of PRLR+ cells compared with the PCI-6B cell line. (B) Immunocytochemical staining of SCCHN cell lines (magnification × 400). Positive membranous and cytoplasmic PRLR staining (red colour of Cy3) is shown for the PCI-6A cell line, whereas the PCI-6B cell line is negative. Nuclei are counterstained with Hoechst dye (blue). (C) Immunoprecipitation reveals a prominent band between 75 and 80 kD, corresponding to the PRLR protein in the lysate of PCI-6A cells, whereas only a weak band was detected in the lysate of PCI-6B cells. Immunoglobulin G (IgG) heavy chain was used as a loading control and T47D cell line served as a positive control.
Mentions: The PRLR expression was initially assessed in SCCHN cell lines (n=8) established from primary tumours and the corresponding metastases from four patients. The breast cancer cell line T47D served as the positive control. The PRLR expression was determined in the SCCHN lines by flow cytometry and immunocytochemistry. Of the eight SCCHN lines, five (4A, 4B, 6A, 37A, 37B) were positive for PRLR expression (Table 3). The only pair of SCCHN cell lines with a heterogeneous PRLR expression profile was PCI-6A and PCI-6B (Figure 1A). The majority of PCI-6A cells, which had been generated from a primary tumour, were highly PRLR positive, whereas all PCI-6B cells generated from a metachronously developed corresponding lymph node metastasis were negative for PRLR, both on the cell surface and in the cytoplasm (Figure 1B). To substantiate the specificity of PRLR staining results, we examined PRLR expression in the SCCHN cell lines PCI-6A and PCI-6B using immunoprecipitation. In accordance with data obtained from immunocytochemistry and flow cytometry, PRLR immunoprecipitation resulted in a prominent band at 80 kDa that corresponded to the PRLR-predicted molecular weight using lysate from PCI-6A cells, whereas only a weak band was detected in PCI-6B cell lysate (Figure 1C). To exclude the possibility that the divergent PRLR expression profiles of PCI-6A and PCI-6B cells might be because of culture selection, we evaluated PRLR expression in sections of the primary tumour and the metachronously developed lymph node metastasis by immunohistochemistry (Figure 2). The results from these samples confirmed the data obtained from the cell lines. To further validate the results obtained with the SCCHN lines, we examined 13 tissue specimens of primary and metastatic SCCHNs randomly selected from the institutional tumour tissue archive. Breast tissue specimens known to express PRLR served as control. Of 13 SCCHN specimens, 9 (69%) were positive for PRLR expression based on the intensity of PRLR staining and the distribution of positive cells (data not shown).

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