Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone

Roudier, Martine P.; True, Lawrence D.; Higano, Celestia S.; Vesselle, Hubert; Ellis, William; Lange, Paul H.; Vessella, Robert L.

doi:10.1016/s0046-8177(03)00190-4

Cited by 280 publications

(266 citation statements)

References 18 publications

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“…PCa heterogeneity has also been demonstrated by examining gene expression profiles 32 and patterns of metastasis. 33 Thus, diversity in PCa progression is a reflection of different phenotypes. 34 Some prostate cancers exhibit an indolent course, even without therapy.…”

Section: Discussionmentioning

confidence: 99%

Determining Prostate Cancer-Specific Death through Quantification of Stromogenic Carcinoma Area in Prostatectomy Specimens

Ayala

Müezzínoğlu

Hammerich

et al. 2011

The American Journal of Pathology

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We previously reported that reactive stroma grading in prostate cancer (PCa) is predictive of biochemical recurrence in prostatectomies and biopsies. In this study, we tested whether quantifying the percentage of reactive stromal grade 3 (RSG 3; stromogenic carcinoma pattern) in the entire tumor is predictive of PCa-specific death. Whole-mount prostatectomies operated by a single surgeon obtained between 1983 and 1998 were reviewed. Reactive stroma was evaluated as described previously, and areas of RSG 3 in the entire tumor were registered as percentages of total tumor. Statistical analysis was performed using Spearman, Kaplan-Meier, and Cox analyses. In all, 872 cases were Prostate cancer (PCa) remains the most common malignancy affecting men and is the second-leading cause of cancer-related death of men in the United States. 1,2 The most accepted and internationally used histological classification to predict the behavior of PCa is the Gleason scoring system. 3-7 Tools such as the Kattan nomogram or the Partin tables combine predictive information to optimize the prediction of time to biochemical recurrence (BCR). 8 -11 However, all of these histological parameters examine the epithelial component of the cancer, and not the interaction between the tumor and the host.The most common histological interaction between the tumor and the native host stroma in many tumors is desmoplasia, or reactive stroma (RS). Reactive stroma in PCa was described in our previous studies and characterized at the phenotypic, 12-15 morphological, 16,17 and genomic levels. 18 We immunophenotyped RS as cells coexpressing vimentin and smooth muscle ␣-actin, with loss of terminal muscle differentiation markers such as desmin and/or calponin. Other studies described RS as a mixture of fibroblasts, myofibroblasts, endothelial cells, and immune cells in breast cancer. 19 -21 We recently demonstrated that RS is promising as a new marker to predict a patient's time to progression in PCa, using both biopsies and tissue microarrays from radical prostatectomy specimens. [12][13][14] To determine whether RS carries predictive information, we charac-

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Section: Discussionmentioning

confidence: 99%

Determining Prostate Cancer-Specific Death through Quantification of Stromogenic Carcinoma Area in Prostatectomy Specimens

Ayala

Müezzínoğlu

Hammerich

et al. 2011

The American Journal of Pathology

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“…Prostate cancer metastases occur earliest and most frequently-though not exclusively-in bone and are commonly associated with an osteoblastic response. [1][2][3][4] Because of this phenomenon, great effort has gone into determining its biological basis with the aim of identifying a suitable treatment strategy. One investigational therapy designed to address this involves blockade of the endothelin signaling axis with ETA antagonists.…”

Section: Introductionmentioning

confidence: 99%

Bone-specific growth inhibition of prostate cancer metastasis by Atrasentan

Drake

Danke

Henry

2010

Cancer Biology & Therapy

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“…It is important to better understand the role of neuroendocrine differentiation of prostate cancer since the greater the proportion of neuroendocrine phenotype accompanying prostate adenocarcinoma, the poorer the prognosis for the patient and the greater the likelihood that the tumor will progress to androgen independence [3][4][5]. Also, some metastases from conventional ductal prostate cancers exhibit a neuroendocrine phenotype [6]. Recent research shows that, a NE-10 allograft model (established from the 12T-10 transgenic model of NE prostate cancer), will promote growth of the LNCaP xenograft in castrated mice [7].…”

Section: Introductionmentioning

confidence: 99%

Neuroendocrine differentiation in the 12T‐10 transgenic prostate mouse model mimics endocrine differentiation of pancreatic beta cells

et al. 2007

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BACKGROUND. Neuroendocrine (NE) prostate cancer develops as an aggressive disease that does not respond to androgen ablation therapy. It has been demonstrated that the paracrine action of NE cells facilitates the progression of androgen dependent adenocarcinoma to an androgen independent state, suggesting a significant role for NE cells during failure of androgen ablation therapy. METHODS. To investigate the pathways that are involved in NE differentiation of prostate cancer, we have looked at the expression of genes known to be involved in endocrine differentiation of b-cells in the pancreas. This study has been performed using the NE prostate cancer mouse model (12T-10) and the derivative allograft model (NE-10). RESULTS. Immunohistochemical studies have shown that the neuroendocrine prostate tumors express the transcription factors Foxa2, mouse achaete-scute homolog-1 (mash-1), neurogenin3 (Ngn3) and Nkx2.2. These tumors show a loss of hairy/enhancer of split (Hes-1), a gene that inhibits NE differentiation. Human NE prostate cancers also express Foxa2 and human achaete-scute homolog-1 (HASH-1). These genes are expressed in NE prostate tumors in the similar sequential manner as they appear in a pancreatic b-cell endocrine differentiation. Foxa2 expression is detected in early prostatic intraepithelial neoplasia (PIN). Mash-1 expression is detected in a few clusters within low grade PIN lesions and Nkx2.2 expression is rarely detected in individual scattered cells within the PIN lesion. Ngn3 and Nkx2.2 frequently appear in the invasive NE cancer. Subsequent NE metastasis to lung and liver show a distinct gene expression pattern. The lung metastasis expresses Ngn3 but does not express Nkx2.2 whereas liver metastases do not express Ngn3 but express Nkx2.2. CONCLUSIONS. These results suggest that Ngn3 and Nkx2.2 expression are markers for sitespecific metastasis and/or transcriptionally regulated genes that are required for organ-specific Abbreviations: NE, neuroendocrine; NED, neuroendocrine differentiation; PIN, prostatic intraepithelial neoplasia; AR, androgen receptor; RT-PCR, reverse transcription-polymerase chain reaction;LGPIN, low grade prostatic intraepithelial neoplasia, HGPIN, high grade prostatic intraepithelial neoplasia.

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Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone

Cited by 280 publications

References 18 publications

Determining Prostate Cancer-Specific Death through Quantification of Stromogenic Carcinoma Area in Prostatectomy Specimens

Determining Prostate Cancer-Specific Death through Quantification of Stromogenic Carcinoma Area in Prostatectomy Specimens

Bone-specific growth inhibition of prostate cancer metastasis by Atrasentan

Neuroendocrine differentiation in the 12T‐10 transgenic prostate mouse model mimics endocrine differentiation of pancreatic beta cells

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