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Differential expression of CD10 in prostate cancer and its clinical implication

Dall'Era MA, True LD, Siegel AF, Porter MP, Sherertz TM, Liu AY - BMC Urol (2007)

Bottom Line: Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study.Increased staining for CD10 was associated with PSA recurrence after RP.CD13 staining did not correlate significantly with any of these same clinical parameters.

Affiliation: Department of Urology, University of Washington, Seattle, WA, USA. mdallera@urology.ucsf.edu

ABSTRACT

Background: CD10 is a transmembrane metallo-endopeptidase that cleaves and inactivates a variety of peptide growth factors. Loss of CD10 expression is a common, early event in human prostate cancer; however, CD10 positive cancer cells frequently appear in lymph node metastasis. We hypothesize that prostate tumors expressing high levels of CD10 have a more aggressive biology with an early propensity towards lymph node metastasis.

Methods: Eighty-seven patients, 53 with and 34 without pathologically organ confined prostate cancer at the time of radical prostatectomy (RP), were used for the study. Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study. Serial sections from available frozen tumor specimens in OCT were processed for CD10 immunohistochemistry. Cancer glands were graded for the presence and intensity of CD10 staining, and overall percentage of glands staining positive was estimated. Clinical characteristics including pre- and post-operative PSA and Gleason score were obtained. A similar study as a control for the statistical analysis was performed with CD13 staining. For statistical analysis, strong staining was defined as > 20% positivity based on the observed maximum separation of the cumulative distributions.

Results: CD10 expression significantly correlated with Gleason grade, tumor stage, and with pre-operative serum PSA. Seventy percent of RP specimens from patients with node metastasis showed strong staining for CD10, compared to 30% in the entire cohort (OR = 3.4, 95% CI: 1.08-10.75, P = 0.019). Increased staining for CD10 was associated with PSA recurrence after RP. CD13 staining did not correlate significantly with any of these same clinical parameters.

Conclusion: These results suggest that the expression of CD10 by prostate cancer corresponds to a more aggressive phenotype with a higher malignant potential, described histologically by the Gleason score. CD10 offers potential clinical utility for stratifying prostate cancer to predict biological behavior of the tumor.

CD10 and CD13 prostate cancer cell types. Positive staining is indicated by the brown chromogen deposit. Non-cancer glands are generally positive for both CD10 and CD13. In the left and middle cases the tumors consist of small crowded glands in the left half of the field. Most of the cancer glands are CD10- and CD13+, although a few isolated CD10+ cancer glands can be seen. In the right case, a subpopulation of CD13+ cancer cells are present in the larger population of CD10-/CD13- cancer cells. This tumor shows no glandular morphology. Magnification is 20×.
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Figure 1: CD10 and CD13 prostate cancer cell types. Positive staining is indicated by the brown chromogen deposit. Non-cancer glands are generally positive for both CD10 and CD13. In the left and middle cases the tumors consist of small crowded glands in the left half of the field. Most of the cancer glands are CD10- and CD13+, although a few isolated CD10+ cancer glands can be seen. In the right case, a subpopulation of CD13+ cancer cells are present in the larger population of CD10-/CD13- cancer cells. This tumor shows no glandular morphology. Magnification is 20×.

Mentions: Both CD10 and CD13 are expressed by luminal cells of the prostatic epithelium but their expression in cancer is heterogeneous [1]. Examples of all four possible CD10/CD13 cancer cell types – CD10-/CD13-, CD10-/CD13+, CD10+/CD13-, CD10+/CD13+ – were detected in our cohort. Normal epithelium present in the specimens showed the characteristic strong CD10 and CD13 expression at the luminal plasma membrane. Fig. 1 shows frozen section examples of tumors stained serially for CD10 and CD13. In all three cases, the cancer glands were mostly negative for CD10. In two cases, the cancer glands were positive for CD13, and a small subpopulation of CD13+ tumor cells was present in one case. These examples showed that CD13+ cancer cells could be found in tumors with either a glandular (Gleason 3) or non-glandular (Gleason 4) morphology. Overall, the predominant cancer cell phenotype was CD10-/CD13-, and this was validated by DNA array analysis data shown in Fig. 2. As can be seen, the expression pattern was similar for CD13 and CD10 (except in the cancer cell lines) with both CD10 and CD13 expression down-regulated in cancer specimens. For the cell lines, the expression profiles of these two genes were in agreement with the reported flow cytometry and immunocytochemistry data [11,16]. The data also showed that expression of any particular gene was variable in cancer; one cancer cell type may express it while another one may not. Their differential expression in cell lines may reflect the situation in tumors, where either positive or negative cancer cell types are found.

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Differential expression of CD10 in prostate cancer and its clinical implication

Dall'Era MA, True LD, Siegel AF, Porter MP, Sherertz TM, Liu AY - BMC Urol (2007)

CD10 and CD13 prostate cancer cell types. Positive staining is indicated by the brown chromogen deposit. Non-cancer glands are generally positive for both CD10 and CD13. In the left and middle cases the tumors consist of small crowded glands in the left half of the field. Most of the cancer glands are CD10- and CD13+, although a few isolated CD10+ cancer glands can be seen. In the right case, a subpopulation of CD13+ cancer cells are present in the larger population of CD10-/CD13- cancer cells. This tumor shows no glandular morphology. Magnification is 20×.
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Figure 1: CD10 and CD13 prostate cancer cell types. Positive staining is indicated by the brown chromogen deposit. Non-cancer glands are generally positive for both CD10 and CD13. In the left and middle cases the tumors consist of small crowded glands in the left half of the field. Most of the cancer glands are CD10- and CD13+, although a few isolated CD10+ cancer glands can be seen. In the right case, a subpopulation of CD13+ cancer cells are present in the larger population of CD10-/CD13- cancer cells. This tumor shows no glandular morphology. Magnification is 20×.
Mentions: Both CD10 and CD13 are expressed by luminal cells of the prostatic epithelium but their expression in cancer is heterogeneous [1]. Examples of all four possible CD10/CD13 cancer cell types – CD10-/CD13-, CD10-/CD13+, CD10+/CD13-, CD10+/CD13+ – were detected in our cohort. Normal epithelium present in the specimens showed the characteristic strong CD10 and CD13 expression at the luminal plasma membrane. Fig. 1 shows frozen section examples of tumors stained serially for CD10 and CD13. In all three cases, the cancer glands were mostly negative for CD10. In two cases, the cancer glands were positive for CD13, and a small subpopulation of CD13+ tumor cells was present in one case. These examples showed that CD13+ cancer cells could be found in tumors with either a glandular (Gleason 3) or non-glandular (Gleason 4) morphology. Overall, the predominant cancer cell phenotype was CD10-/CD13-, and this was validated by DNA array analysis data shown in Fig. 2. As can be seen, the expression pattern was similar for CD13 and CD10 (except in the cancer cell lines) with both CD10 and CD13 expression down-regulated in cancer specimens. For the cell lines, the expression profiles of these two genes were in agreement with the reported flow cytometry and immunocytochemistry data [11,16]. The data also showed that expression of any particular gene was variable in cancer; one cancer cell type may express it while another one may not. Their differential expression in cell lines may reflect the situation in tumors, where either positive or negative cancer cell types are found.

Bottom Line: Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study.Increased staining for CD10 was associated with PSA recurrence after RP.CD13 staining did not correlate significantly with any of these same clinical parameters.

Affiliation: Department of Urology, University of Washington, Seattle, WA, USA. mdallera@urology.ucsf.edu

ABSTRACT

Background:

Background: CD10 is a transmembrane metallo-endopeptidase that cleaves and inactivates a variety of peptide growth factors. Loss of CD10 expression is a common, early event in human prostate cancer; however, CD10 positive cancer cells frequently appear in lymph node metastasis. We hypothesize that prostate tumors expressing high levels of CD10 have a more aggressive biology with an early propensity towards lymph node metastasis.

Methods: Eighty-seven patients, 53 with and 34 without pathologically organ confined prostate cancer at the time of radical prostatectomy (RP), were used for the study. Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study. Serial sections from available frozen tumor specimens in OCT were processed for CD10 immunohistochemistry. Cancer glands were graded for the presence and intensity of CD10 staining, and overall percentage of glands staining positive was estimated. Clinical characteristics including pre- and post-operative PSA and Gleason score were obtained. A similar study as a control for the statistical analysis was performed with CD13 staining. For statistical analysis, strong staining was defined as > 20% positivity based on the observed maximum separation of the cumulative distributions.

Results: CD10 expression significantly correlated with Gleason grade, tumor stage, and with pre-operative serum PSA. Seventy percent of RP specimens from patients with node metastasis showed strong staining for CD10, compared to 30% in the entire cohort (OR = 3.4, 95% CI: 1.08-10.75, P = 0.019). Increased staining for CD10 was associated with PSA recurrence after RP. CD13 staining did not correlate significantly with any of these same clinical parameters.

Conclusion: These results suggest that the expression of CD10 by prostate cancer corresponds to a more aggressive phenotype with a higher malignant potential, described histologically by the Gleason score. CD10 offers potential clinical utility for stratifying prostate cancer to predict biological behavior of the tumor.

View Similar Images In: Results  - Collection
View Article: Medline Plus - Pubmed Central - HTML -  PubMed
Show All Figures - Show MeSH
getmorefigures.php?pmc=1829163&rFormat=json&query=null&req=5