Different clinical roles for p21-activated kinase-1 in primary and recurrent ovarian carcinoma

Ben Davidson, Ie Ming Shih, Tian-Li Wang

Research output: Contribution to journalArticle

Abstract

We recently found amplification of chromosome 11q13.5 in high-grade ovarian serous carcinoma. In the present study, we analyzed the protein expression and clinical significance of p21-activated kinase-1, one of the genes amplified at this site. Formalin-fixed paraffin-embedded sections from 186 effusions (152 peritoneal, 34 pleural) were immunostained. p21-Activated kinase-1 expression in tumor cells was analyzed for possible association with clinicopathologic parameters and survival. The association between protein expression of p21-activated kinase-1 and Rsf-1, a chromatin remodeling protein whose gene colocalizes with p21-activated kinase-1, was additionally studied. p21-Activated kinase-1 protein expression was found in carcinoma cells in 158 (85%) of 186 effusions. Of these, 62 (39%) stained weakly and 96 (61%) strongly. p21-Activated kinase-1 was coexpressed with Rsf-1 (P = .006). Specimens from patients diagnosed with International Federation of Gynecology and Obstetrics stage IV disease had higher staining intensity compared with stage III tumors (P = .014). Univariate survival analysis for patients with primary diagnosis prechemotherapy effusions demonstrated a significant association between higher p21-activated kinase-1 staining extent and longer overall survival (P = .024). In addition, higher staining extent (P = .015) and intensity (P = .013) correlated with better progression-free survival. In contrast, higher p21-activated kinase-1 staining extent correlated with poor overall survival in disease recurrence postchemotherapy effusions (P = .044). In Cox analysis, higher p21-activated kinase-1 staining extent independently correlated with longer progression-free survival (P = .016) and shorter overall survival (.049) in primary diagnosis and disease recurrence effusions, respectively. p21-Activated kinase-1 is frequently expressed in ovarian carcinoma cells in effusions and is associated with opposite prognostic role in primary and recurrent disease. This suggests altered cellular function for this kinase along disease progression, possibly chemotherapy mediated.

Original languageEnglish (US)
Pages (from-to)1630-1636
Number of pages7
JournalHuman Pathology
Volume39
Issue number11
DOIs
StatePublished - Nov 2008

Fingerprint

p21-Activated Kinases
Carcinoma
Staining and Labeling
Survival
Disease-Free Survival
Proteins
Recurrence
Chromatin Assembly and Disassembly
Ascitic Fluid
Survival Analysis
Gynecology
Paraffin
Formaldehyde
Obstetrics
Disease Progression
Neoplasms
Phosphotransferases
Chromosomes

Keywords

  • Disease recurrence
  • Effusions
  • Ovarian carcinoma
  • Primary diagnosis
  • Survival

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Different clinical roles for p21-activated kinase-1 in primary and recurrent ovarian carcinoma. / Davidson, Ben; Shih, Ie Ming; Wang, Tian-Li.

In: Human Pathology, Vol. 39, No. 11, 11.2008, p. 1630-1636.

Research output: Contribution to journalArticle

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abstract = "We recently found amplification of chromosome 11q13.5 in high-grade ovarian serous carcinoma. In the present study, we analyzed the protein expression and clinical significance of p21-activated kinase-1, one of the genes amplified at this site. Formalin-fixed paraffin-embedded sections from 186 effusions (152 peritoneal, 34 pleural) were immunostained. p21-Activated kinase-1 expression in tumor cells was analyzed for possible association with clinicopathologic parameters and survival. The association between protein expression of p21-activated kinase-1 and Rsf-1, a chromatin remodeling protein whose gene colocalizes with p21-activated kinase-1, was additionally studied. p21-Activated kinase-1 protein expression was found in carcinoma cells in 158 (85{\%}) of 186 effusions. Of these, 62 (39{\%}) stained weakly and 96 (61{\%}) strongly. p21-Activated kinase-1 was coexpressed with Rsf-1 (P = .006). Specimens from patients diagnosed with International Federation of Gynecology and Obstetrics stage IV disease had higher staining intensity compared with stage III tumors (P = .014). Univariate survival analysis for patients with primary diagnosis prechemotherapy effusions demonstrated a significant association between higher p21-activated kinase-1 staining extent and longer overall survival (P = .024). In addition, higher staining extent (P = .015) and intensity (P = .013) correlated with better progression-free survival. In contrast, higher p21-activated kinase-1 staining extent correlated with poor overall survival in disease recurrence postchemotherapy effusions (P = .044). In Cox analysis, higher p21-activated kinase-1 staining extent independently correlated with longer progression-free survival (P = .016) and shorter overall survival (.049) in primary diagnosis and disease recurrence effusions, respectively. p21-Activated kinase-1 is frequently expressed in ovarian carcinoma cells in effusions and is associated with opposite prognostic role in primary and recurrent disease. This suggests altered cellular function for this kinase along disease progression, possibly chemotherapy mediated.",
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AB - We recently found amplification of chromosome 11q13.5 in high-grade ovarian serous carcinoma. In the present study, we analyzed the protein expression and clinical significance of p21-activated kinase-1, one of the genes amplified at this site. Formalin-fixed paraffin-embedded sections from 186 effusions (152 peritoneal, 34 pleural) were immunostained. p21-Activated kinase-1 expression in tumor cells was analyzed for possible association with clinicopathologic parameters and survival. The association between protein expression of p21-activated kinase-1 and Rsf-1, a chromatin remodeling protein whose gene colocalizes with p21-activated kinase-1, was additionally studied. p21-Activated kinase-1 protein expression was found in carcinoma cells in 158 (85%) of 186 effusions. Of these, 62 (39%) stained weakly and 96 (61%) strongly. p21-Activated kinase-1 was coexpressed with Rsf-1 (P = .006). Specimens from patients diagnosed with International Federation of Gynecology and Obstetrics stage IV disease had higher staining intensity compared with stage III tumors (P = .014). Univariate survival analysis for patients with primary diagnosis prechemotherapy effusions demonstrated a significant association between higher p21-activated kinase-1 staining extent and longer overall survival (P = .024). In addition, higher staining extent (P = .015) and intensity (P = .013) correlated with better progression-free survival. In contrast, higher p21-activated kinase-1 staining extent correlated with poor overall survival in disease recurrence postchemotherapy effusions (P = .044). In Cox analysis, higher p21-activated kinase-1 staining extent independently correlated with longer progression-free survival (P = .016) and shorter overall survival (.049) in primary diagnosis and disease recurrence effusions, respectively. p21-Activated kinase-1 is frequently expressed in ovarian carcinoma cells in effusions and is associated with opposite prognostic role in primary and recurrent disease. This suggests altered cellular function for this kinase along disease progression, possibly chemotherapy mediated.

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KW - Survival

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