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Can cyclin D1 be utilized as a second step “after basal cell marker” for both diagnosis and prognosis of prostatic adenocarcinoma?

Ihab Shafek Atta, Aly Gomaa Eid, Mohamed Atta El-Hag, Faisal Fahd AlQahtani.

Background: Cyclin D1 is involved in regulating cell cycle as well as cancer progression and its overexpression is incriminated in the pathogenesis of many tumors including prostatic adenocarcinoma (PAC). One of the basal cell markers is p63. p63 is a nuclear protein, which plays a critical role in the growth and development of many epithelial organs. p63 is confined to basal cells of squamous epithelia and urothelium, as well as basal cells of many organs including, prostate. So, confirmation of the presence or absence of basal cell layer is the first clue to deny or ascertain the diagnosis of PAC.

Objective: To investigate the expression of cyclin D1 with p63 in both benign prostatic hyperplasia (BPH) and PAC and correlate the results of cyclin D1 with both Gleason ‘s score and clinical staging.

Materials and Methods: Retrospective evaluation of archived specimens of BPH and PAC and p63 was used for more confirmation of the histopathological state. This study was done in 60 cases of BPH and 60 cases of PAC. All cases were stained for p63 before staining with cyclin D1 antibody. All immunohistochemical analyses were performed on routinely processed, formalin-fixed, paraffin-embedded tissue. Any degree of reactivity was considered positive. Percentage of positive cells was calculated and scored as follows: + (weak) = less than 10%, ++ (moderate) = 11% to 50%, and +++ (strong) = more than 50% tumor cells stained positive. Immunohistochemical expressions were correlated with Gleason grade as well as staging of PAC in an attempt to recognize the prognostic value of cyclin D1.

Result: Cyclin D1 was expressed in 13% and 93% of BPH and PAC cases, respectively, opposite to 92% and 4% in that of p63. In PAC cases, the degree of cyclin D1 reactivity was increased in high Gleason’s grade with significant correlation (P = 0.043). Also a significant correlation was obtained between the degree of staining and the staging of PAC (P = 0.045).

Conclusion: Cyclin D1 is highly expressed in PAC cases and its overexpression was seen in high Gleason’s score and staging beyond T2.

Key words: Benign prostatic hyperplasia, cyclin D1, immunohistochemistry, prostatic adenocarcinoma, p63

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