Prognostic implications of p21 (Waf1/Cip1) immunolocalization in multiple myeloma

Ohata, Masahiko; Nakamura, Shinobu; Fujita, Hiroyuki; Isemura, Mamoru

doi:10.2220/biomedres.26.91

Cited by 16 publications

(8 citation statements)

References 20 publications

(33 reference statements)

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“…This two-faced nature of CDKN1A seems to be dependent on its cellular location. Several IHC studies imply that nuclear expression of CDKN1A indicates its tumor-suppressive role, while its presence in the cytoplasm favors an oncogenic role [25,[51][52][53][54]. We have observed a significant correlation between CN loss, decreased CDKN1A expression and poor prognosis, suggesting a tumor suppressive role of CDKN1A in chRCC.…”

Section: Discussionsupporting

confidence: 53%

Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients

Ohashi

Angori

Batavia

et al. 2020

Cancers

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Chromophobe renal cell carcinoma (chRCC) patients have good prognosis. Only 5%–10% patients die of metastatic disease after tumorectomy, but tumor progression cannot be predicted by histopathological parameters alone. chRCC are characterized by losses of many chromosomes, whereas gene mutations are rare. In this study, we aim at identifying genes indicating chRCC progression. A bioinformatic approach was used to correlate chromosomal loss and mRNA expression from 15287 genes from The Cancer Genome Atlas (TCGA) database. All genes in TCGA chromophobe renal cancer dataset (KICH) for which a significant correlation between chromosomal loss and mRNA expression was shown, were identified and their associations with outcome was assessed. Genome-wide DNA copy-number alterations were analyzed by Affymetrix OncoScan® CNV FFPE Microarrays in a second cohort of Swiss chRCC. In both cohorts, tumors with loss of chromosomes 2, 6, 10, 13, 17 and 21 had signs of tumor progression. There were 4654 genes located on these chromosomes, and 13 of these genes had reduced mRNA levels, which was associated with poor outcome in chRCC. Decreased CDKN1A expression at mRNA (p = 0.02) and protein levels (p = 0.02) were associated with short overall survival and were independent predictors of prognosis (p < 0.01 and <0.05 respectively). CDKN1A expression status is a prognostic biomarker independent of tumor stage. CDKN1A immunohistochemistry may be used to identify chRCC patients at greater risk of disease progression.

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Section: Discussionsupporting

confidence: 53%

Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients

Ohashi

Angori

Batavia

et al. 2020

Cancers

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“…Recent studies also suggested that p21 WAF1 upregulation correlated positively with tumor grade, invasiveness, and aggressiveness, and was a poor prognostic indicator in other carcinomas. [13][14][15][16][17][18][19][20][21][22][23][24][25] Consequently, p21 WAF1 was often misregulated in human cancers, but its expression, depending on the cellular context and circumstances, suggested that it could act as a tumor suppressor [13][14][15][16][17][18][19] or as an oncogene. [20][21][22][23][24][25] The results of these studies were paradoxical evidently.…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic relevance of p21WAF1 in stage III esophageal squamous cell carcinoma

Liu

et al. 2011

Diseases of the Esophagus

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The prognostic effect of p21(WAF1) expression on esophageal squamous cell carcinoma patients is controversial. Further clarifying the effect of this protein is beneficial for optimizing the patient outcomes. In the current study, we investigated the expression of p21(WAF1) protein in 189 specimens of stage III ESCC by immunohistochemistry. As shown by the Kaplan-Meier curve, the overall survival rate of the positive-expression group was significantly higher than that of the negative-expression group (P < 0.05). No significant correlation was observed between p21(WAF1) expression and clinicopathological parameters in terms of gender, age, tumor location, tumor grade, pathological stage, and number of regional lymph node metastases (P > 0.05). We concluded that p21(WAF1) played an intricate role in the tumorigenesis and development of ESCC. p21(WAF1) could serve as a positive prognostic predictor for stage III ESCC patients.

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“…The contribution of protein localization within cells to pathologies is not unprecedented. For example, the nuclear to cytoplasmic ratios of β-catenin [50–52], p63 [53], p21 [54], p27 Kip1 [55, 56] and p53 [57] contribute to cellular transformation.…”

Section: Discussionmentioning

confidence: 99%

A Shift from Nuclear to Cytoplasmic Breast Cancer Metastasis Suppressor 1 Expression Is Associated with Highly Proliferative Estrogen Receptor-Negative Breast Cancers

Frolova¹,

Edmonds²,

Bodenstine³

et al. 2009

Tumor Biol

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Background/Aims: To determine breast cancer metastasis suppressor 1 (BRMS1) expression in breast cancers and the efficacy of BRMS1 as a prognostic indicator, BRMS1 expression was assessed in two sets of breast cancer tissues. Methods: Epithelial cells from 36 frozen samples of breast cancers and corresponding normal breast were collected by laser capture microdissection and assessed for BRMS1 by quantitative RT-PCR and immunohistochemistry. BRMS1 was also evaluated by immunohistochemistry in a tissue microarray of 209 breast cancers and correlated with indicators of prognosis [estrogen receptor (ER), progesterone receptor (PR), ErbB2, p53, p27^Kip1, Bcl2 and Ki-67]. Results: BRMS1 mRNA and protein were higher in 94 and 81%, respectively, of breast cancers than in corresponding normal epithelium. BRMS1 localization was predominantly nuclear, but 60–70% of cancers also exhibited cytoplasmic immunostaining. Breast cancers with lower nuclear than cytoplasmic BRMS1 (nuclear score – cytoplasmic score ≤0; 11% of cancers) had lower ER, lower PR and higher Ki-67 expression. There was also a trend toward poorer overall survival in this group of cancers, but this was only of borderline significance (p = 0.073). In Cox proportional hazards models, loss of nuclear BRMS1 was not a significant predictor of overall survival. Conclusions: Loss of nuclear BRMS1 was associated with ER-negative cancers and a high rate of proliferation, but was not an independent indicator of prognosis.

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Prognostic implications of p21 (Waf1/Cip1) immunolocalization in multiple myeloma

Cited by 16 publications

References 20 publications

Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients

Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients

Expression and prognostic relevance of p21WAF1 in stage III esophageal squamous cell carcinoma

A Shift from Nuclear to Cytoplasmic Breast Cancer Metastasis Suppressor 1 Expression Is Associated with Highly Proliferative Estrogen Receptor-Negative Breast Cancers

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