Neuroendocrine Differentiation In Prostate Adenocarcinoma Biopsies And Its Correlation To Histological Grading

Neuroendocrine Differentiation In Prostate Adenocarcinoma Biopsies And Its Correlation To Histological Grading

MĂDĂLINA MARCU⁽¹⁾, E. RADU⁽²⁾, MARIA SAJIN⁽¹⁾

Text Prostate adenocarcinoma is one of the most frequent malignant diseases in men. Patients are stratified according to disease extension: organ-confined cancer (pT1, T2) benefits of definitive therapy (radical prostatectomy, radiotherapy, neoadjuvant therapy), while extraprostatic tumor extension or metastasis are an indication for hormone therapy. Androgen deprivation of malignant cells is well established for the treatment of metastatc disease, recurrence after radical prostatectomy or radiotherapy and as neoadjuvant therapy. However, 18 to 36 month after an initial response to hormone therapy, most of the prostate carcinomas swich to a hormone resistant phenotype, entering into a more aggressive and ultimately fatal stage of disease [1].

Neuroendocrine (NE) cells are a distinct epithelial cell compartment of the normal human prostate gland. Their phenotype and range of endocrine secretion products are similar, but not identical to those of NE-like cells from prostate carcinoma. Neuroendocrine differentiation (NED) is seen in virtually all cases of prostatic carcinoma, mostly in a focal pattern; a number of studies pointed out that its extent is associated to hormone therapy refractory and aggressive disease. Yet neuroendocrine differentiation is included by the College of American Pathologists Consensus Statement 1999 in category III of prognostic and predictive factors (not sufficiently studied to demonstrate prognostic value) [2].

In prostate cancer extending beyond the organ limits, most of the studies pointed out a strog association between the extent of NE differentiation and aggressive disease, but there are conflicting conclusions regarding the value of NED as an independent prognostic factor. Increased NE differentiation was found to be associated with aggressive disease [3, 4], Gleason score [5, 6], anti-androgen thearpy failure [3] and survival [6, 7]. However, McWilliam concluded that detection of neuroendocrine differentiation in conventional prostatic adenocarcinoma is not an independent indicator of prognosis [6].

Only a few studies addressed the prognostic significance of NE differentiation in localized prostate cancer, and data collected on prostatic biopsies is even scarcer. Some results indicate that histological grade and NE differentiation seen in prostatectomy samples predicted progression in multivariate analysis [8] or disease specific survival [9]. NE differentiation was also considered an additional prognostic marker in radical prostatectomy samples [10] and a factor that significantly aggravate established adverse prognostic parameters such as nodal status, tumour stage, pretherapeutic PSA-level, and Gleason score [11]. However, other studies lead to diverging conclusions: the extent of neuroendocrine differentiation was not foud to be an independent prognostic factor for biochemical failure of therapy in multivariate analysis [12, 13].

Screening population at risk using serum PSA monitoring and clinical examination recently gained in frequency, leading to an increase in the proportion of low-grade adenocarcinoma that is diagnosed on prostate core biopsy. New prognostic factors would help identifying at this stage patients at risk for unfavorable evolution, that would benefit from alternate therapy. This study aims to find correlations between the extent of neurocrine differentiation and known factors of disease evolution such as histological grade, malignant cell proliferation and serum PSA levels.