Molecular prostate cancer pathology: Current issues and achievements

Schalken, Jack A.; Bergh, Anders; Bono, Aldo; Foster, Christopher S.; Gospadarowicz, Mary; Isaacs, William B.; Rubin, Mark A.; Schröder, Fritz H.; Tribukait, Bernhard; Tsukamotot, Taiji; Wiklund, Peter

doi:10.1080/03008880510030950

Cited by 18 publications

(9 citation statements)

References 39 publications

(39 reference statements)

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“…Although, nomograms based on pre- and post-operative parameters offer some information about patients’ prognosis, limited knowledge about which CaP is likely to progress, as well as, when it will recur severely impedes individualized selection of therapy and subsequent prediction of outcome [23]. Recent studies have shown that chemokines, cytokines and other proteins that are associated with inflammatory processes may function in promoting tumor invasion and metastasis [24–26]. Furthermore, some of these molecules, such as cyclooxygease-2 have shown prognostic potential for predicting CaP progression [18].…”

Section: Discussionmentioning

confidence: 99%

Osteopontin and Interleukin-8 Expression is Independently Associated with Prostate Cancer Recurrence

Caruso¹,

Carmack²,

Lokeshwar

et al. 2008

Clinical Cancer Research

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Purpose: Lack of reliable biomarkers limits accurate prediction of prostate-specific antigen biochemical recurrence (disease progression) in prostate cancer. The two inflammatory chemokines, osteopontin and interleukin-8 (IL-8), are associated with tumor angiogenesis and metastasis. We investigated whether osteopontin and IL-8 expression in prostate cancer correlates with disease progression. Experimental Design: Archival prostatectomy specimens (n = 103) were obtained from patients with minimum 72-month follow-up. Osteopontin and IL-8 expression was evaluated by immunohistochemistry and graded for intensity and the area. Association of osteopontin and IL-8 staining with biochemical recurrence was evaluated by univariate and multivariate models. Results: In tumor cells, osteopontin and IL-8 staining was higher in the recurred group (203.2 F 78.4; 181.1 F 89.3) than in the nonrecurred group (122.7 F 76.6; 96.4 F 85.6; P < 0.001). Higher osteopontin and IL-8 staining was also observed in benign areas adjacent to tumor in the recurred group, than in nonrecurred group. In univariate analysis, except age, all preoperative and postoperative variables and osteopontin and IL-8 staining scores were significantly associated with biochemical recurrence (P < 0.05). In multivariate analysis, margin status and osteopontin staining independently associated with biochemical recurrence within 72 months. Osteopontin, either alone or with IL-8 and seminal vesicle invasion, was a significant variable in predicting biochemical recurrence within 24 months. Osteopontin and IL-8 staining predicted recurrence with high sensitivity (75.5%; 73.6%) and specificity (76%; 70.6%). Conclusion: In prostatectomy specimens, osteopontin expression is independently associated with biochemical recurrence. Both osteopontin and IL-8 may be predictors of early disease progression.

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Section: Discussionmentioning

confidence: 99%

Osteopontin and Interleukin-8 Expression is Independently Associated with Prostate Cancer Recurrence

Caruso¹,

Carmack²,

Lokeshwar

et al. 2008

Clinical Cancer Research

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“…This complicates diagnosis and therapy, because it is not sufficient to detect tumors, but also necessary to distinguish forms of the disease requiring palliative treatment, definitive therapy, or active monitoring, respectively. Moreover, since definitive therapy can be performed by surgery or irradiation and may be supplemented by antiandrogenic therapy and cytotoxic chemotherapy depending on the circumstances of each individual case, criteria for optimal selection of therapy are desirable [2].…”

mentioning

confidence: 99%

Epigenetics of prostate cancer: beyond DNA methylation

Schulz

Hatina

2006

J Cellular Molecular Medi

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Prostate cancer is the most or second-most frequent non-cutaneous cancer of males in Western industrialized countries [1] and a major cause of suffering and mortality. In spite of substantial progress in research, diagnosis and treatment, the disease remains characterized by puzzles. Epigenetics AbstractEpigenetic mechanisms permit the stable inheritance of cellular properties without changes in DNA sequence or amount. In prostate carcinoma, epigenetic mechanisms are essential for development and progression, complementing, amplifying and diversifying genetic alterations. DNA hypermethylation affects at least 30 individual genes, while repetitive sequences including retrotransposons and selected genes become hypomethylated. Hypermethylation of several genes occurs in a coordinate manner early in carcinogenesis and can be exploited for cancer detection, whereas hypomethylation and further hypermethylation events are associated with progression. DNA methylation alterations interact with changes in chromatin proteins. Prominent alterations at this level include altered patterns of histone modification, increased expression of the EZH2 polycomb histone methyltransferase, and changes in transcriptional corepressors and coactivators. These changes may make prostate carcinoma particularly susceptible to drugs targeting chromatin and DNA modifications. They relate to crucial alterations in a network of transcription factors comprising ETS family proteins, the androgen receptor, NKX3.1, KLF, and HOXB13 homeobox proteins. This network controls differentiation and proliferation of prostate epithelial cells integrating signals from hormones, growth factors and cell adhesion proteins that are likewise distorted in prostate cancer. As a consequence, prostate carcinoma cells appear to be locked into an aberrant state, characterized by continued proliferation of largely differentiated cells. Accordingly, stem cell characteristics of prostate cancer cells appear to be secondarily acquired. The aberrant differentiation state of prostate carcinoma cells also results in distorted mutual interactions between epithelial and stromal cells in the tumor that promote tumor growth, invasion, and metastasis.

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“…Other preoperative factors may improve the predictive accuracy for pathologic stage, including neuroendocrine (NE) differentiation, nuclear DNA content, and MVD [36,66] (Table 7). …”

Section: Prognostic Molecular Markers (And Methods)mentioning

confidence: 99%

“…The discovery of new molecular markers that, in a needle biopsy setting, are of prognostic significance is very much the need of the hour (Table 7) [58,66].…”

Section: Other Molecular Markersmentioning

confidence: 99%

Histopathology reporting of prostate needle biopsies. 2005 update

et al. 2006

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This report reviews the diagnostic and prognostic importance of the pathologic findings in prostate needle biopsies. The morphological findings of the needle biopsy may be placed into one of the following five categories: prostate cancer, atypical small acinar proliferation, high-grade prostatic intraepithelial neoplasia, inflammation, and benign prostatic tissue. While the prime goal of the biopsy is to diagnose prostatic adenocarcinoma, once carcinoma is detected, further descriptive information regarding the type, amount of cancer, and grade forms the cornerstone for contemporary management of the patient and for assessment of the potential for local cure and the risk for distant metastasis. The information provided in the needle biopsy report regarding the attributes of carcinoma is used depending on the individual patient's medical condition and preference and on the treating physician's evaluation to determine whether any form of treatment is indicated and, if so, the type of therapy.

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Molecular prostate cancer pathology: Current issues and achievements

Cited by 18 publications

References 39 publications

Osteopontin and Interleukin-8 Expression is Independently Associated with Prostate Cancer Recurrence

Osteopontin and Interleukin-8 Expression is Independently Associated with Prostate Cancer Recurrence

Epigenetics of prostate cancer: beyond DNA methylation

Histopathology reporting of prostate needle biopsies. 2005 update

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