Dedifferentiation in the metastatic progression of prostate carcinoma

Abstract

BACKGROUND Dedifferentiation is a distinctive feature of cancer progression. Detailed histologic analysis of primary prostate carcinoma and synchronous lymph node metastases may improve our understanding of the complex process of cancer progression and metastasis. METHODS The authors studied 242 regional lymph node positive prostate carcinoma patients who underwent radical prostatectomy and bilateral lymphadenectomy between 1987 and 1992 at the Mayo Clinic. Patients ranged in age from 47–79 years (median, 66 years). The median follow‐up was 6.1 years. Gleason scores of lymph node metastases and primary tumors were compared and correlated with systemic disease progression. Histologic dedifferentiation was defined as a higher Gleason grade in the lymph node metastases than in the primary tumor. Systemic disease progression was defined as the presence of distant metastases documented by biopsies, abdominal computed tomography, plain radiograph, or bone scan. RESULTS The 5‐year systemic progression free survival (PFS) rate was 90%. The Gleason score in the lymph node metastases was higher than in the primary tumor in 45% of patients, lower in 12% of patients, and matched exactly in 43% of patients. The 5‐year PFS was significantly different between patients with histologic dedifferentiation (88% ± 3) and those without dedifferentiation (94% ± 2) (P = 0.04). Adjusting for the Gleason grade of the primary tumor and total lymph node tumor volume, the relative risk for disease progression associated with dedifferentiation was 1.8 (95% confidence interval, 0.7–4.7; P = 0.25). CONCLUSIONS The findings of the current study demonstrate the morphologic heterogeneity of metastases from prostate carcinoma. There is a trend toward histologic dedifferentiation when prostate carcinoma metastasizes to regional lymph nodes. This dedifferentiation, although univariately significant, was not associated with disease progression when adjusted for lymph node tumor volume. Cancer 1999;86:657–63. © 1999 American Cancer Society.

Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome

“…Similar to previous work from Boorman et al . and others, we identified patients with higher nodal ISUP‐G to have worse outcomes for all oncological parameters assessed. Cribriform pattern 4 did not show any association with adverse outcome when identified in the node in contradistinction to its known impact when present in prostatectomy material.…”

“…The prostatectomy and nodal ISUP‐G correlated poorly with only 30% of cases having the same ISUP‐G. Similarly, Cheng et al found only 43% concordance between Gleason scores in the prostate and nodes ( n = 242) . This is in contrast to Hofer et al ( n = 119), who reported similar Gleason patterns in both the prostate and the nodes and found the nodal metastases to be so homogeneous in their group as to not warrant assigning a second Gleason pattern .…”

“…While prostate cancer grading is applied to prostatic tissue, no such morphological grading has been proposed or validated for assessment of nodal metastases. A handful of papers have examined the impact of Gleason grade in prostatic nodal metastases, with varying results . In the contemporary practice of urological pathology, it is now recognised that the presence of intraductal carcinoma (IDC) and cribriform type pattern 4 (CC) are morphological features conferring adverse prognosis in the prostate .…”

NFIB Mediates BRN2 Driven Melanoma Cell Migration and Invasion Through Regulation of EZH2 and MITF

“…This role for BRN2 in facilitating a less differentiated phenotype has been observed in sub-sets of cells within melanoma tumours that are known to be more invasive (Pinner et al, 2009). The concept that cells undergo a process of de-differentiation to a more stem-cell like phenotype to help enhance metastasis has been well documented in various cancer models (Cheng et al, 1999, Friedmann-Morvinski and Verma, 2014, Sell, 1993). Immunostaining of NFIB within both mouse xenograft and human primary/metastatic melanoma tumours shows clear co-localization with BRN2 expressing populations, indicating that NFIB expression within melanoma tumours is most likely linked with these more undifferentiated and invasive cellular populations previously associated with BRN2 expression (Goodall et al, 2008, Pinner et al, 2009).…”

Lymph node staging in prostate cancer: perspective for the pathologist

“…Similarly, Boormans et al 56 found a Gleason Score >7 within the LN metastasis to be a predictor of survival. Other studies could not corroborate the independent prognostic value of nodal Gleason Score when controlled for other factors 62 63. Consequently, it is not necessary to routinely report these parameters.…”