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Increased expression of class III beta-tubulin in castration-resistant human prostate cancer.

Terry S, Ploussard G, Allory Y, Nicolaiew N, Boissière-Michot F, Maillé P, Kheuang L, Coppolani E, Ali A, Bibeau F, Culine S, Buttyan R, de la Taille A, Vacherot F - Br. J. Cancer (2009)

Bottom Line: Overexpression of betaIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies.Whereas moderate-to-strong betaIII-tubulin expression was detected in only 3 out of 74 (4%) hormone-naive tumour specimens obtained from patients who never received hormone therapy, 6 out of 24 tumour specimens (25%) from patients treated for 3 months with neoadjuvant hormone therapy and 24 out of 40 (60%) castration-resistant tumour specimens from chronic hormone-treated patients were found to express significant levels of betaIII-tubulin.These findings were supported by in vitro and in vivo settings.

View Article: PubMed Central - PubMed

Affiliation: INSERM, Unité 955, Créteil F-94000, France. stephane.terry@inserm.fr

ABSTRACT

Background: Class III beta-tubulin (betaIII-tubulin) is expressed in tissues of neuronal lineage and also in several human malignancies, including non-small-cell lung carcinoma, breast and ovarian cancer. Overexpression of betaIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies. At present, betaIII-tubulin expression remains largely uncharacterised in prostate cancer.

Methods: In this report, we evaluated the expression of betaIII-tubulin in 138 different human prostate tumour specimens by immunohistochemistry from patients with hormone-treated or hormone-untreated prostate cancer. betaIII-tubulin expression was also examined in various prostatic cancer cell lines including in androgen-sensitive human prostate cancer cells, LNCaP, grown in androgen-depleted medium in 2D cultures or as tumour xenografts when the host mouse was castrated.

Results: Whereas moderate-to-strong betaIII-tubulin expression was detected in only 3 out of 74 (4%) hormone-naive tumour specimens obtained from patients who never received hormone therapy, 6 out of 24 tumour specimens (25%) from patients treated for 3 months with neoadjuvant hormone therapy and 24 out of 40 (60%) castration-resistant tumour specimens from chronic hormone-treated patients were found to express significant levels of betaIII-tubulin. These findings were supported by in vitro and in vivo settings.

Conclusion: Our data indicate that betaIII-tubulin expression is augmented in prostate cancer by androgen ablation and that the expression of this beta-tubulin isoform is associated with the progression of prostate cancer to the castration-resistant state, a stage largely responsible for mortality from prostate cancer.

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βIII-tubulin expression in prostate cancers. (A–C) Representative tissue microarray element, regular section or biopsy sample stained with antibody to βIII-tubulin with immunostains showing the absence of staining in hormone-naive prostate cancer (panel A) and strong staining in primary (panel B) and metastatic (panel C) castration-resistant refractory prostate cancers. (D and E) Representative consecutive sections stained with antibodies to βIII-tubulin (panel D) or NSE (panel E). Immunostainings show concomitant βIII-tubulin and NSE expression in prostate cancer cells. (F) Prostatic small cell carcinoma showing strong immunoreactivity for βIII-tubulin. Original magnification × 200; inset, × 25.
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fig1: βIII-tubulin expression in prostate cancers. (A–C) Representative tissue microarray element, regular section or biopsy sample stained with antibody to βIII-tubulin with immunostains showing the absence of staining in hormone-naive prostate cancer (panel A) and strong staining in primary (panel B) and metastatic (panel C) castration-resistant refractory prostate cancers. (D and E) Representative consecutive sections stained with antibodies to βIII-tubulin (panel D) or NSE (panel E). Immunostainings show concomitant βIII-tubulin and NSE expression in prostate cancer cells. (F) Prostatic small cell carcinoma showing strong immunoreactivity for βIII-tubulin. Original magnification × 200; inset, × 25.

Mentions: In the HNPC group, accounting for more than half of the specimens, the presence of βIII-tubulin expression in cancer cells was relatively rare (Table 1 and Figure 1A). Of these 74 cases, 67 were scored as completely negative (0) and only 3 cases (4%) were considered to be positive, scoring from moderate-to-strong for βIII-tubulin in the cancer cells. With the exception of occasional stained cells in the basal compartment, βIII-tubulin expression was not detected in either normal basal cells or luminal prostate epithelial cells present in these specimens. The extremely small number of positively stained specimens in this group prevented us from deriving any statistically reliable association with other patient prognostic factors. Of the 24 cases of HTPC evaluated in our study, 6 (25%) were considered to be positive with βIII-tubulin immunoreactivity in the moderate-to-strong range in more than 10% of cancer cells (Table 1). Nine cases of HTPC showed complete negative (0) staining, whereas nine other cases in this category were scored as weak or contained only rare (<10%) tumour cells positively stained, and this later group was also recorded as negative. For the overall HTPC group, βIII-tubulin expression was found to be significantly higher when compared with the HNPC group as evaluated by Fisher's exact test applying the Bonferroni correction (P=0.0186).


Increased expression of class III beta-tubulin in castration-resistant human prostate cancer.

Terry S, Ploussard G, Allory Y, Nicolaiew N, Boissière-Michot F, Maillé P, Kheuang L, Coppolani E, Ali A, Bibeau F, Culine S, Buttyan R, de la Taille A, Vacherot F - Br. J. Cancer (2009)

βIII-tubulin expression in prostate cancers. (A–C) Representative tissue microarray element, regular section or biopsy sample stained with antibody to βIII-tubulin with immunostains showing the absence of staining in hormone-naive prostate cancer (panel A) and strong staining in primary (panel B) and metastatic (panel C) castration-resistant refractory prostate cancers. (D and E) Representative consecutive sections stained with antibodies to βIII-tubulin (panel D) or NSE (panel E). Immunostainings show concomitant βIII-tubulin and NSE expression in prostate cancer cells. (F) Prostatic small cell carcinoma showing strong immunoreactivity for βIII-tubulin. Original magnification × 200; inset, × 25.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2743364&req=5

fig1: βIII-tubulin expression in prostate cancers. (A–C) Representative tissue microarray element, regular section or biopsy sample stained with antibody to βIII-tubulin with immunostains showing the absence of staining in hormone-naive prostate cancer (panel A) and strong staining in primary (panel B) and metastatic (panel C) castration-resistant refractory prostate cancers. (D and E) Representative consecutive sections stained with antibodies to βIII-tubulin (panel D) or NSE (panel E). Immunostainings show concomitant βIII-tubulin and NSE expression in prostate cancer cells. (F) Prostatic small cell carcinoma showing strong immunoreactivity for βIII-tubulin. Original magnification × 200; inset, × 25.
Mentions: In the HNPC group, accounting for more than half of the specimens, the presence of βIII-tubulin expression in cancer cells was relatively rare (Table 1 and Figure 1A). Of these 74 cases, 67 were scored as completely negative (0) and only 3 cases (4%) were considered to be positive, scoring from moderate-to-strong for βIII-tubulin in the cancer cells. With the exception of occasional stained cells in the basal compartment, βIII-tubulin expression was not detected in either normal basal cells or luminal prostate epithelial cells present in these specimens. The extremely small number of positively stained specimens in this group prevented us from deriving any statistically reliable association with other patient prognostic factors. Of the 24 cases of HTPC evaluated in our study, 6 (25%) were considered to be positive with βIII-tubulin immunoreactivity in the moderate-to-strong range in more than 10% of cancer cells (Table 1). Nine cases of HTPC showed complete negative (0) staining, whereas nine other cases in this category were scored as weak or contained only rare (<10%) tumour cells positively stained, and this later group was also recorded as negative. For the overall HTPC group, βIII-tubulin expression was found to be significantly higher when compared with the HNPC group as evaluated by Fisher's exact test applying the Bonferroni correction (P=0.0186).

Bottom Line: Overexpression of betaIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies.Whereas moderate-to-strong betaIII-tubulin expression was detected in only 3 out of 74 (4%) hormone-naive tumour specimens obtained from patients who never received hormone therapy, 6 out of 24 tumour specimens (25%) from patients treated for 3 months with neoadjuvant hormone therapy and 24 out of 40 (60%) castration-resistant tumour specimens from chronic hormone-treated patients were found to express significant levels of betaIII-tubulin.These findings were supported by in vitro and in vivo settings.

View Article: PubMed Central - PubMed

Affiliation: INSERM, Unité 955, Créteil F-94000, France. stephane.terry@inserm.fr

ABSTRACT

Background: Class III beta-tubulin (betaIII-tubulin) is expressed in tissues of neuronal lineage and also in several human malignancies, including non-small-cell lung carcinoma, breast and ovarian cancer. Overexpression of betaIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies. At present, betaIII-tubulin expression remains largely uncharacterised in prostate cancer.

Methods: In this report, we evaluated the expression of betaIII-tubulin in 138 different human prostate tumour specimens by immunohistochemistry from patients with hormone-treated or hormone-untreated prostate cancer. betaIII-tubulin expression was also examined in various prostatic cancer cell lines including in androgen-sensitive human prostate cancer cells, LNCaP, grown in androgen-depleted medium in 2D cultures or as tumour xenografts when the host mouse was castrated.

Results: Whereas moderate-to-strong betaIII-tubulin expression was detected in only 3 out of 74 (4%) hormone-naive tumour specimens obtained from patients who never received hormone therapy, 6 out of 24 tumour specimens (25%) from patients treated for 3 months with neoadjuvant hormone therapy and 24 out of 40 (60%) castration-resistant tumour specimens from chronic hormone-treated patients were found to express significant levels of betaIII-tubulin. These findings were supported by in vitro and in vivo settings.

Conclusion: Our data indicate that betaIII-tubulin expression is augmented in prostate cancer by androgen ablation and that the expression of this beta-tubulin isoform is associated with the progression of prostate cancer to the castration-resistant state, a stage largely responsible for mortality from prostate cancer.

Show MeSH
Related in: MedlinePlus