Novel markers for poor prognosis in head and neck cancer

Chin, David Y.; Boyle, Glen M.; Williams, Rebecca M.; Ferguson, Kaltin; Pandeya, Nirmala; Pedley, Julie; Campbell, Catherine; Theile, David E.; Parsons, Peter G.; Coman, William B.

doi:10.1002/ijc.20608

Cited by 147 publications

(122 citation statements)

References 25 publications

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“…INK4a (45)(46)(47)(48)(49)(50)(51)(52) or p21 WAF1/CIP1 (17,(21)(22)(23)(24)51). Nevertheless, this is a controversial issue, with other researchers reporting a relationship between these proteins and survival (9,(18)(19)(20)53).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of p21WAF1/CIP1, p16INK4a and CD44s in tongue cancer

González‐Moles

Gil-Montoya²,

Ruiz‐Ávila³

et al. 2007

Oncol Rep

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Abstract. The role of lost or reduced expression of p21, p16 and CD44s in the survival of tongue cancer patients was investigated. Tumours and adjacent non-tumour epithelia (ANTE) from 36 patients with tongue cancer were retrospectively studied by immunohistochemistry using monoclonal antibodies against p21, p16 and CD44s proteins. Expression of p21, p16 and CD44s and their relationship with clinical and pathological parameters were analyzed. Of 36 patients, 12 (33.33%) developed recurrence and 12 died of the disease (mean survival, 25.5 months). In four cases (11.1%), concomitant low expression (<50% of tumour cells) of p21, p16 and CD44s was detected but had no effect on survival or recurrence in the univariate analysis. In the multivariate analysis, low expression of CD44s was the sole prognostic factor related to survival (p=0.01, hazards ratio: 0.749). There was no expression of p21, p16 or CD44s in ANTE from 3 out of 24 cases studied, and this finding was related to recurrence in the univariate analysis. In the multivariate analysis, low expression of CD44s in ANTE was again the sole factor related to recurrence (p=0.002, hazards ratio: 0.028). In conclusion, low expression of CD44s is related to tumour cell invasiveness and may be of clinical relevance as a prognostic factor. IntroductionCellular programs of proliferation, differentiation, senescence and apoptosis are closely linked to cell cycle regulation, and alterations of the cell cycle machinery have been described as a hallmark of cancer development (1). Molecular mechanisms controlling progression through the restriction point (R), such as the retinoblastoma protein (pRB), are of paramount importance in this context (2). Hypophosphorylated pRB inhibits S phase entry (cell arrest near R point) by forming complexes with E2F transcription factors that actively repress transcription of DNA synthesis-regulating genes (3). Upon pRB phosphorylation, pRB/E2F complexes are disrupted and E2F can activate these promoters, allowing the advance of cells to late G1 and DNA synthesis. Therefore, pRB or members of this regulatory pathway are critical molecular targets for malignant transformation, and there is growing evidence that the pRB pathway is rendered dysfunctional in oral cancer (2). Down-regulation of p16INK4a , a member of the INK family of CDK inhibitors (CDKis), has been described in oral cancer, and p16INK4a inactivation is believed to be an early event in oral carcinogenesis (4-8). Some authors reported that loss of p16INK4a is correlated with a poor prognosis in oral cancer patients (9-11), whereas others found no relationship with survival (12). In addition, some studies found loss of p21 WAF1/CIP1 , a member of CIP/KIP family of CDKis, to be a very early event in oral carcinogenesis (13)(14)(15)(16)(17). However, the prognostic significance of p21 WAF1/CIP1 expression is controversial, with several studies identifying it as a prognostic factor (18-20) and others finding no association (17,(21)(22)(23)(24).Besides alterations in their cell-cycle ...

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of p21WAF1/CIP1, p16INK4a and CD44s in tongue cancer

González‐Moles

Gil-Montoya²,

Ruiz‐Ávila³

et al. 2007

Oncol Rep

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“…SPARC is known to interact with other matrix molecules such as collagen I, vitronectin and thrombospondin and with integrin-linked kinase (Rosenblatt et al, 1997;Barker et al, 2005a) and SPARCdeficient cells were recently found to exhibit defective DNA nuclear excision repair (Kato et al, 2005). Elevated SPARC expression has been found in many human malignancies including prostate, breast, colon, hepatocellular, head and neck, and non-small-cell lung carcinomas (Le Bail et al, 1999;Thomas et al, 2000;Lussier et al, 2001;Koukourakis et al, 2003;Jones et al, 2004;Chin et al, 2005). In prostate carcinoma, SPARC expression in cancer cells is associated with bone metastasis (Thomas et al, 2000).…”

Section: Functional Characterization Of St7 Cs-f Hooi Et Almentioning

confidence: 99%

ST7-mediated suppression of tumorigenicity of prostate cancer cells is characterized by remodeling of the extracellular matrix

et al. 2006

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Multiple lines of evidence have provided compelling evidence for the existence of a tumor suppressor gene (TSG) on chromosome 7q31.1. ST7 may be the target of this genetic instability but its designation as a TSG is controversial. In this study, we show that, functionally, ST7 behaves as a tumor suppressor in human cancer. ST7 suppressed growth of PC-3 prostate cancer cells inoculated subcutaneously into severe combined immunodeficient mice, and increased the latency of tumor detection from 13 days in control tumors to 23 days. Re-expression of ST7 was also associated with suppression of colony formation under anchorage-independent conditions in MDA-MB-231 breast cancer cells and ST7 mRNA expression was downregulated in 44% of primary breast cancers. Expression profiling of PC-3 cells revealed that ST7 predominantly induces changes in genes involved in re-modeling the extracellular matrix such as SPARC, IGFBP5 and several matrix metalloproteinases. These data indicate that ST7 may mediate tumor suppression through modification of the tumor microenvironment.

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“…Subsequently, caveolin-1 activation leads to invagination of the cell membrane to form transcytotic vesicles called caveolae, which transport albumin (and nab-P) across the endothelial cell to the interstitial space [13]. The albumin-binding matricellular protein SPARC (secreted protein, acidic and rich in cysteine), which is often over-expressed in many tumors, may also contribute to the higher intratumoral concentration of nab-P. SPARC has been associated with a poor prognosis in multiple tumors, including squamous cell cancer of the head and neck, Non-small cell lung carcinoma and breast cancer [14][15][16]. The amount of SPARC over-expression and the role SPARC may have in the increased intratumoral uptake or sequestration of nab-P is an area of active investigation in various malignancies.…”

Section: Chemistrymentioning

confidence: 99%