The dedifferentiation of metastatic prostate carcinoma

Abstract

Summary Two hundred consecutive staging lymphadenectomies with metastatic prostate adenocarcinoma and 100 consecutive autopsies with widely disseminated metastatic prostate adenocarcinoma were identified. The metastases from 41% of the staging lymphadenectomies were entirely differentiated (gland forming) and an additional 43% were predominantly (50% or more) differentiated. In contrast, the metastases from 70% of the autopsies were entirely undifferentiated (non-gland forming) and an additional 18% were predominantly undifferentiated. Further, five patients with completely or predominantly differentiated metastases in staging lymphadenectomies were found to have widespread completely or predominantly undifferentiated metastases at autopsy 4-7 years later. These findings suggest that dedifferentiation occurs within metastases and that dedifferentiation within metastases may be important in understanding the widespread dissemination of metastatic prostate carcinoma.Dedifferentiation is characterised by a progression from a more differentiated to a less differentiated histological appearance with time. Dedifferentiation has been demonstrated experimentally and clinically within primary tumours but not, as yet, within metastases (Foulds, 1954;Kastendieck & Altenahr, 1976;Nowell, 1976;Brawn, 1983;Barnett & Eccles, 1984;Leonard & Smyth, 1985;Poste, 1986). In order to determine whether dedifferentiation occurs within metastases the current study compared the histology of metastatic prostate carcinoma in staging lymphadenectomies to the histology of widely disseminated prostate carcinoma at autopsy. Materials and methodsEight hundred and fifty-seven consecutive staging lymphadenectomies were performed on patients with a diagnosis of prostate carcinoma. Criteria for staging lymphadenectomy were: (1) confirmed histological diagnosis of prostate carcinoma in needle biopsy or transurethral resection of prostate; (2) prostate carcinoma clinically confined to the prostate, or 6cm or less in size if extending beyond the capsule of the prostate; and (3) no evidence of metastases preoperatively. Two hundred of these 857 staging lymphadenectomies had metastatic prostate carcinoma in pelvic lymph node(s) (obturator, hypogastric, external iliac, internal iliac or common iliac lymph nodes).One hundred consecutive autopsies with widely disseminated metastatic prostate carcinoma were identified. Widely disseminated metastatic prostate carcinoma was defined as metastases beyond lymph nodes and/or bone. Invasions from the prostate into adjacent tissue or organs were not considered to be metastases.Metastases were determined to be of prostatic origin by: (1) the histological appearance of the metastases; (2) a comparison of the histological appearance of the primary tumour and the metastases; (3) the gross description of the prostate; and (4) serum acid phosphatase levels. If doubt remained sections of the tumour were stained with a Prostatic Specific Antigen Immunohistology kit (HistoGeMTM) (Hadji et al., 1981).The current study examin...

Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets

“…Autopsy studies suggest that a subset of patients with prostate cancer die from pure AR- negative NEPC(20–21) but this incidence may be under-recognized. Patients are not typically biopsied late in the stages of PCA to evaluate for NEPC progression, but can be suspected in patients with progressive disease despite a normal or modestly elevated PSA and elevated serum markers of neuroendocrine differentiation (i.e., chromogranin A or NSE)(1).…”

Gleason score, age and screening: Modeling dedifferentiation in prostate cancer

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Weekly chemotherapy in advanced prostatic cancer

“…Considering the great difficulties involved in the assessment of response criteria in advanced prostatic cancer, the use of bone and prostatic tumour markers, together with other evaluation criteria such as performance status, bone pain and a, (Hetherington et al, 1988;Speights, 1989;Jacobs et al, 1980Jacobs et al, ): al., 1991Francini et al, 1992).…”