Prognostic factors for fibromatoses: A correlation of proliferation index, estrogen receptor, p53, retinoblastoma, andsrc gene products and clinical features with outcome

Moffatt, Elizabeth J.; Kerns, Billie‐Jo M.; Madden, John M.; Layfield, Lester J.

doi:10.1002/(sici)1096-9098(199706)65:2<117::aid-jso8>3.0.co;2-a

Cited by 16 publications

(15 citation statements)

References 14 publications

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“…The ER␣ antibody used in the current study, ER-6F11, has been shown to react only with the ␣ form of the ER molecule by Western blot analysis (verbal confirmation received from Novacastra). It is possible that the positive staining noted by Moffatt et al 17 can be attributed to partial crossreactivity of the CC4-5 clone with ER␤.…”

Section: Discussionmentioning

confidence: 92%

“…Assays of tissues containing only ER␤ will result in a falsenegative result, accounting for the historical discrepancy in the literature regarding ER in extraabdominal fibromatoses and other tumors. Of note is the outlier among the immunohistochemical studies: the study by Moffatt et al 17 (Table 2), which used the Ventana automated staining kit for ER, found staining in 15 of 52 cases. The antibody in this kit was provided by Novocastra (Clone CC4-5) and was raised using whole ER␣ protein as the immunogen.…”

Section: Discussionmentioning

confidence: 99%

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Estrogen receptor‐β expression in extraabdominal fibromatoses

Deyrup

Tretiakova

Montag

2005

Cancer

123

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BACKGROUNDEarly experiments using ligand‐binding assays demonstrated the presence of estrogen receptor (ER) in fibromatoses. These findings were not confirmed by later studies using immunohistochemical analysis.METHODSTo verify the expression of ERs in fibromatosis as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, the authors examined a series of 40 extraabdominal fibromatoses using antibodies raised against ERβ.RESULTSAll 40 cases of extraabdominal fibromatosis were at least focally positive for ERβ. Thirty‐three of 40 (83%) displayed 3+ (>50%) expression, 5 of 40 (12%) were 2+ (11–50%), and 2 of 40 (5%) cases showed 1+ (<10%) expression. All cases were negative for ERα.CONCLUSIONSAlthough extraabdominal fibromatosis does not express ERα, there appears to be nearly uniform expression of ERβ. This finding clarifies discrepancies in the literature regarding estrogen expression in fibromatosis, and provides a biological mechanism for the action of antiestrogenic compounds in the treatment of fibromatosis. Estrogen antagonists may have a role in the treatment of refractory or recurrent extraabdominal fibromatoses. Cancer 2006. © 2005 American Cancer Society.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Estrogen receptor‐β expression in extraabdominal fibromatoses

Deyrup

Tretiakova

Montag

2005

Cancer

123

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“…15 Moffatt et al found that 25% of fibromatoses examined expressed p53 and its presence correlated with aggressiveness and recurrence potential of these lesions. 16 The implications of p53 abnormalities in Peyronie's disease are unknown but potentially far-reaching. The question must be raised, why is it that Peyronie's plaques do not progress to malignant lesions as occurs in other cells and tissues that express p53.…”

Section: Discussionmentioning

confidence: 99%

Perturbation of cell cycle regulators in Peyronie’s disease

Branch

Lubrano

et al. 2001

Int J Impot Res

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Peyronie's disease is a fibromatosis of the tunica albuginea, characterized by development of a plaque consisting primarily of collagen. It has been suggested that trauma to the erect penis is the inciting event. More recent research has focused on the cellular events leading to the dysregulated wound healing and plaque formation. Previous work has shown chromosomal aneusomies and this combined with an increased S-phase in plaque derived cell cultures suggests a perturbation in the cell cycle in this condition. The p53 protein has been shown to be an important cell cycle regulator and pro-apoptotic factor. Aberrant p53 function leading to cell immortalization and proliferation has been implicated in several human malignancies. We hypothesized that abnormal p53 function may explain the high proliferative ability of fibroblasts derived from Peyronie's plaques. This study was undertaken to study the presence and function of p53 and its downstream elements (p21, mdm-2) in Peyronie's disease cell cultures. Plaque-derived fibroblasts have been established in culture and characterized. These cells and control neonatal foreskin fibroblasts were subjected to 5 Gy of gamma radiation to induce DNA damage. After fixation, antibodies to p53 and its transcriptional elements were used to stain irradiated and non-irradiated cells and levels of p53, p21 and mdm-2 were quantified using combined immunoflouresence and flow cytometry. Non-irradiated plaque fibroblasts demonstrated the presence of p53, p21 and mdm-2 at baseline. In control foreskin fibroblasts no p53 or mdm-2 were detectable at baseline. In irradiated foreskin-derived cells significant changes in all elements were demonstrated indicating a fully functional p53 pathway and cell cycle checkpoint system in these cells. In contrast, plaquederived cells showed no such alterations in levels of cell cycle regulators following irradiation. This is highly suggestive of an aberration of the p53 pathway in plaque-derived fibroblasts. Peyronie's plaque-derived fibroblasts demonstrated stabilization and defunctionalization of p53 protein combined with appropriate responses of its transcriptional elements. These findings may explain the high cell proliferation rates in these cells and suggests a role for perturbation of the p53 pathway in the pathogenesis of Peyronie's disease.

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“…This supports previous findings from analyses of p53 function in other fibromatoses. 51,52 The implications of p53 abnormalities in Peyronie's disease are unknown but potentially far reaching.…”

Section: Cell Cycle Dysregulationmentioning

confidence: 99%

Expanding the paradigm for plaque development in Peyronie's disease

Mulhall

2003

Int J Impot Res

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Prognostic factors for fibromatoses: A correlation of proliferation index, estrogen receptor, p53, retinoblastoma, andsrc gene products and clinical features with outcome

Cited by 16 publications

References 14 publications

Estrogen receptor‐β expression in extraabdominal fibromatoses

Estrogen receptor‐β expression in extraabdominal fibromatoses

Perturbation of cell cycle regulators in Peyronie’s disease

Expanding the paradigm for plaque development in Peyronie's disease

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