The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma

Boslooper, Karin; Lam, Alfred King‐Yin; Gao, Jin; Weinstein, Stephen R.; Johnson, Newell W.

doi:10.1080/00313020802198010

Cited by 25 publications

(28 citation statements)

References 18 publications

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“…Hence, like other Hsps, alphaB-crystallin interacts with p53 and modulates its function. On the other hand, it is believed that p53 is involved in the regulation of Hsps in cancer and p53 mutations result in an increase of Hsp transcripts [59,60]. Our IHC findings further support these interactions, specifically between the alphaB-crystallin and p53 proteins.…”

Section: Discussionsupporting

confidence: 79%

alphaB-crystallin is a marker of aggressive breast cancer behavior but does not independently predict for patient outcome: a combined analysis of two randomized studies

et al. 2014

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BackgroundalphaB-crystallin is a small heat shock protein that has recently been characterized as an oncoprotein correlating with the basal core phenotype and with negative prognostic factors in breast carcinomas. The purpose of this study was to evaluate alphaB-crystallin with respect to clinicopathological parameters and the outcome of patients with operable high-risk breast cancer.MethodsA total of 940 tumors were examined, derived from an equal number of patients who had participated in two randomized clinical trials (paclitaxel-containing regimen in 793 cases). Immunohistochemistry for ER, PgR, HER2, Ki67, CK5, CK14, CK17, EGFR, alphaB-crystallin, BRCA1 and p53 was performed. BRCA1 mutation data were available in 89 cases.Resultsalphaβ-crystallin was expressed in 170 cases (18.1%) and more frequently in triple-negative breast carcinomas (TNBC) (45% vs. 14.5% non-TNBC, p < 0.001). alphaB-crystallin protein expression was significantly associated with high Ki67 (Pearson chi-square test, p < 0.001), p53 (p = 0.002) and basal cytokeratin protein expression (p < 0.001), BRCA1 mutations (p = 0.045) and negative ER (p < 0.001) and PgR (p < 0.001). Its overexpression, defined as >30% positive neoplastic cells, was associated with adverse overall survival (Wald’s p = 0.046). However, alphaB-crystallin was not an independent prognostic factor upon multivariate analysis. No interaction between taxane-based therapy and aβ-crystallin expression was observed.ConclusionsIn operable high-risk breast cancer, alphaB-crystallin protein expression is associated with poor prognostic features indicating aggressive tumor behavior, but it does not seem to have an independent impact on patient survival or to interfere with taxane-based therapy.Trial registrationsACTRN12611000506998 (HE10/97 trial) and ACTRN12609001036202 (HE10/00 trial).

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Section: Discussionsupporting

confidence: 79%

alphaB-crystallin is a marker of aggressive breast cancer behavior but does not independently predict for patient outcome: a combined analysis of two randomized studies

et al. 2014

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“…Similarly, low CRYAB gene expression was associated with inferior survival in a small cohort of 18 ovarian carcinoma cases (Stronach et al, 2003), although in larger study of 103 ovarian cancer patients, αB-crystallin protein expression was associated with poor relapse-free and overall survival (Volkmann et al, 2013). In a few other studies of diverse tumor types, αB-crystallin expression was not significantly associated with prognosis (Boslooper et al, 2008; Kabbage et al, 2012; Yilmaz et al, 2015). It remains to be determined whether these divergent results reflect differences in study design and/or tumor type.…”

Section: Deregulated Expression In Cancermentioning

confidence: 83%

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

Malin

Petrovič

Strekalova

et al. 2016

Pharmacology & Therapeutics

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αB-crystallin is a widely expressed member of the small heat shock protein family that protects cells from stress by its dual function as a molecular chaperone to preserve proteostasis and as a cell death antagonist that negatively regulates components of the conserved apoptotic cell death machinery. Deregulated expression of αB-crystallin occurs in a broad array of solid tumors and has been linked to tumor progression and poor clinical outcomes. This review will focus on new insights into the molecular mechanisms by which oncogenes, oxidative stress, matrix detachment and other tumor microenvironmental stressors deregulate αB-crystallin expression. We will also review accumulating evidence pointing to an essential role for αB-crystallin in the multi-step metastatic cascade whereby tumor cells colonize distant organs by circumventing a multitude of barriers to cell migration and survival. Finally, we will evaluate emerging strategies to therapeutically target αB-crystallin and/or interacting proteins to selectively activate apoptosis and/or derail the metastatic cascade in an effort to improve outcomes for patients with metastatic disease.

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“…Mutation of p53 is the most common mutation detected in human cancers [57][58][59]. In thyroid cancer, p53 expression was more often noted in undifferentiated carcinoma [38].…”

Section: P53 and P63mentioning

confidence: 99%

Diffuse sclerosing variant of papillary thyroid carcinoma—an update of its clinicopathological features and molecular biology

Pillai

Gopalan

Smith

et al. 2015

Critical Reviews in Oncology/Hematology

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Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is an uncommon variant of papillary thyroid carcinoma. The aim of this review is to critically analyse the features of this entity. A search of the literature revealed 25 clinicopathological studies with in-depth analysis of features of DSVPTC. Overall, the prevalence of DSVPTC varies from 0.7-6.6% of all papillary thyroid carcinoma. Higher prevalence of DSVPTC was noted in paediatric patients and in patients affected by irradiation. DSVPTC tends to occur more frequently in women and in patients in the third decade of life. Macroscopically, DSVPTC can involve the thyroid gland extensively without forming a dominant mass. Microscopic examination of DSVPTC revealed extensive fibrosis, squamous metaplasia and numerous psammoma bodies. The latter pathological feature can aid in the pre-operative diagnosis of the entity by fine needle aspiration and ultrasound. Compared to conventional papillary thyroid carcinoma, DSVPTC had a higher incidence of lymph node metastases at presentation. Distant metastases were noted in approximately 5% of the cases. Patients with DSVPTC were recommended to be managed by aggressive treatment protocols. It is likely that as a result of this, the prognosis of the patients with DSVPTC was noted to be similar to conventional papillary thyroid carcinoma. Overall, cancer recurrence and cancer related mortality have been reported in 14% and 3%, respectively, of patients with DSVPTC. In immunohistochemical studies, DSVPTC showed different expression patterns of epithelial membrane antigen, galectin 3, cell adhesion molecules, p53 and p63 when compared to conventional papillary thyroid carcinoma. On genetic analysis, the occurrence of BRAF and RAS mutations are uncommon events in DSVPTC and activation of RET/PTC rearrangements are common. To conclude, DSVPTC has different clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma.

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The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma

Abstract: The expression of p53 and alpha-B-crystallin were related to the differentiation and site of the HNSCC. Alpha-B-crystallin was not a prognostic marker for HNSCC.

Cited by 25 publications

References 18 publications

alphaB-crystallin is a marker of aggressive breast cancer behavior but does not independently predict for patient outcome: a combined analysis of two randomized studies

alphaB-crystallin is a marker of aggressive breast cancer behavior but does not independently predict for patient outcome: a combined analysis of two randomized studies

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

Diffuse sclerosing variant of papillary thyroid carcinoma—an update of its clinicopathological features and molecular biology

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