Molecular markers for diagnosis and prognosis

Partridge, M; Gaballah, Kamis; Huang, Xiaohong

doi:10.1007/s10555-005-5048-0

Cited by 23 publications

(19 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The benefits of a quantitative, cytopathologic approach to diagnosis have driven the search for molecular-based changes in cancer cells (19). However, no unequivocal molecular marker for early oral cancer detection has yet been identified (2,19).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Oral Cancer Diagnosis by Mechanical Phenotyping

Remmerbach

Wottawah²,

Dietrich³

et al. 2009

Cancer Research

279

219

View full text Add to dashboard Cite

Oral squamous cell carcinomas are among the 10 most common cancers and have a 50% lethality rate after 5 years. Despite easy access to the oral cavity for cancer screening, the main limitations to successful treatment are uncertain prognostic criteria for (pre-)malignant lesions. Identifying a functional cellular marker may represent a significant improvement for diagnosis and treatment. Toward this goal, mechanical phenotyping of individual cells is a novel approach to detect cytoskeletal changes, which are diagnostic for malignant change. The compliance of cells from cell lines and primary samples of healthy donors and cancer patients was measured using a microfluidic optical stretcher. Cancer cells showed significantly different mechanical behavior, with a higher mean deformability and increased variance. Cancer cells (n % 30 cells measured from each patient) were on average 3.5 times more compliant than those of healthy donors [D normal = (4.43 F 0.68) 10 À3 Pa À1 ; D cancer = (15.8 F 1.5) 10À3 Pa À1 ; P < 0.01]. The diagnosis results of the patient samples were confirmed by standard histopathology. The generality of these findings was supported by measurements of two normal and four cancer oral epithelial cell lines. Our results indicate that mechanical phenotyping is a sensible, label-free approach for classifying cancer cells to enable broad screening of suspicious lesions in the oral cavity. It could in principle be applied to any cancer to aid conventional diagnostic procedures.

show abstract

Section: Discussionmentioning

confidence: 99%

“…However, no unequivocal molecular marker for early oral cancer detection has yet been identified (2,19). Analyzing the global cell compliance combines many different possible molecular events, which renders it more robust.…”

Section: Discussionmentioning

confidence: 99%

Oral Cancer Diagnosis by Mechanical Phenotyping

Remmerbach

Wottawah²,

Dietrich³

et al. 2009

Cancer Research

279

219

View full text Add to dashboard Cite

show abstract

“…Despite intensive curative treatment strategies, such as surgery and postoperative radiotherapy, 20 -40% of all patients will develop a locoregional recurrence (LRR) and the 5-year overall survival rate remains B50% (Le Tourneau et al, 2008). For this reason, attempts have been made to identify molecular markers that are able to improve the identification of tumours that will develop LRR and thus might benefit from more aggressive treatment strategies (Partridge et al, 2005). One of the potential prognostic factors is the epidermal growth factor receptor (EGFR), which has been identified as an important prognostic marker in several other cancer types (Mellon et al, 1995;Fischer-Colbrie et al, 1997;Inada et al, 1999;Kersemaekers et al, 1999;Galizia et al, 2006).…”

mentioning

confidence: 99%

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

et al. 2010

View full text Add to dashboard Cite

BACKGROUND: For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5-year overall survival rate is B50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer. METHODS: The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy. RESULTS: In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: 2.2, 95% CI: 1.1 -4.6; P ¼ 0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.2 -27.4; P ¼ 0.03) and extranodal spread (HR: 2.7; 95% CI: 1.2 -6.5; P ¼ 0.02). In vitro clonogenic radiosensitivity assays confirmed that overexpression of PTEN resulted in increased radioresistance. CONCLUSION: Our study is the first report showing that expression of PTEN mediates radiosensitivity in vitro and that increased expression in advanced HNSCC predicts worse LRC.

show abstract

“…The strength of this approach is that p53 gene mutations are the most frequently detected aberration associated with head and neck carcinomas (15). However, although the presence of p53 mutations in the deep margins must signify carcinoma, if contamination has been avoided, the presence of the these mutations in mucosal margins may signify tumor, but these aberrations are also present in dysplasia and may be detected in oral mucosa that looks normal morphologically (10,12,16).…”

mentioning

confidence: 99%

p53 Mutations in Deep Tissues Are More Strongly Associated with Recurrence than Mutation-Positive Mucosal Margins

Huang¹,

Pateromichelakis²,

Hills³

et al. 2007

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Application of ultrasensitive diagnostics has shown that small numbers of p53 mutation-positive cells may signify the presence of residual tumor in histologically normal tissues after resection of squamous cell carcinomas arising in the head and neck area. To date, most studies in this area have focused on analysis of tissues at the mucosal aspect of the resection and highlighted the importance of molecular changes in the field with respect to the risk of recurrence. Experimental Design: In the present investigation, we analyzed normal tissues from mucosal and deep surgical margins, referred to as ''molecular margins,'' for the presence of the signature p53 mutation identified for each tumor. Results:The p53 mutation status of these carcinomas did not correlate with clinical or histopathologic variables, but these mutations provided an excellent target for ultrasensitive analysis of margin status. We found that 11of 16 (68%) of cases with histologically tumor-free (including 9 without dysplasia), but with p53 mutation-positive molecular margins, developed recurrence.The probability of developing local recurrence was significantly higher for the group with p53 mutation-positive margins when compared with the group with clear margins (P = 0.048) and more strongly associated with p53 mutation-positive deep molecular margins than mutation-positive mucosal molecular margins or positivity at both sites (P = 0.009). Conclusions: This shows that although persistent mucosal fields may contribute to recurrence, clonal p53 mutations in deep tissues are an important cause of treatment failure, and molecular margins from both sites should be analyzed in future prospective series.

show abstract

Molecular markers for diagnosis and prognosis

Cited by 23 publications

References 64 publications

Oral Cancer Diagnosis by Mechanical Phenotyping

Oral Cancer Diagnosis by Mechanical Phenotyping

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

p53 Mutations in Deep Tissues Are More Strongly Associated with Recurrence than Mutation-Positive Mucosal Margins

Contact Info

Product

Resources

About