PTEN expression and morphological patterns in prostatic adenocarcinoma

Abstract

Aims Cribriform morphology, which includes intraductal carcinoma (IDCP) and invasive cribriform carcinoma, is an indicator of poor prognosis in prostate cancer. Phosphatase and tensin homologue (PTEN) loss is a predictor of adverse clinical outcomes. The association between PTEN expression and morphological patterns of prostate cancer is unclear. Methods and results We explored the association between PTEN expression by immunohistochemistry, Gleason pattern 4 morphologies, IDCP and biochemical recurrence (BCR) in 163 radical prostatectomy specimens. IDCP was delineated from invasive cribriform carcinoma by p63 positive immunohistochemical staining in basal cells. Combined invasive cribriform carcinoma and IDCP were associated with a higher cumulative incidence of BCR [hazard ratio (HR) = 5.06; 2.21, 11.6, P < 0.001]. When including PTEN loss in the analysis, invasive cribriform carcinoma remained predictive of BCR (HR = 3.72; 1.75, 7.94, P = 0.001), while PTEN loss within invasive cribriform carcinoma did not. Glomeruloid morphology was associated with lower odds of cancer stage pT3 and lower cumulative incidence of BCR (HR = 0.27; 0.088, 0.796, P = 0.018), while PTEN loss within glomeruloid morphology was associated with a higher cumulative incidence of BCR (HR = 4.07; 1.04, 15.9, P = 0.043). Conclusions PTEN loss within glomeruloid pattern was associated with BCR. The presence of any cribriform pattern was associated with BCR, despite PTEN loss not significantly associated with invasive cribriform carcinoma. We speculate that other drivers independent from PTEN loss may contribute to poor prognostic features in cribriform carcinoma.

Intraductal Carcinoma of the Prostate as a Cause of Prostate Cancer Metastasis: A Molecular Portrait

“…Besides the above-mentioned study by Risbringer et al [121], few groups have addressed the molecular features underlying the aggressivity of IDC-P [30,[128][129][130] (Table 5). Increasing our knowledge in this field will be central to the development of new therapies for men with IDC-P.…”

“…Very recently, Spieker et al [130] identified PTEN loss in 86% of IDC-P cases (30/35 RPs) and in 64% of CC lesions (72/112 RPs). In this study, CC was associated with shorter time to biochemical recurrence (multivariate HR: 3.50, 95% CI: 1.89-6.49, p < 0.001) but not IDC-P alone.…”

Current conundrums with cribriform prostate cancer

“…Both entities can show a cribriform pattern of growth, and although they often coexist, studies have shown that there are concrete differences between the two. 6,7 Separating IDCP from invasive cribriform cancer often requires immunohistochemistry to determine the presence of basal cells, which would be seen in IDCP. Staining for the presence of basal cells in all areas of a tumor with cribriform morphology to distinguish IDCP from invasive cribriform cancer is both time-consuming and has additional costs.…”

“…This may be problematic, as some studies have shown a difference in prognosis when separating the two. 7,8,9 A study by Spieker et al showed that a combination of IDCP and invasive cribriform cancer was an independent prognostic indicator for biochemical recurrence. 7 However, when splitting the two entities, only invasive cribriform cancer remained statistically significant, while IDCP did not.…”

“…7,8,9 A study by Spieker et al showed that a combination of IDCP and invasive cribriform cancer was an independent prognostic indicator for biochemical recurrence. 7 However, when splitting the two entities, only invasive cribriform cancer remained statistically significant, while IDCP did not. 7 Additionally, some studies also suggest that there may be genomic alterations associated with one, but not the other histologic feature.…”