1.Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece
Squamous cell carcinoma is further divided according to tumour location into four subtypes:
Except of conventional methods, various ancillary techniques provide information about a tumour that cannot be obtained by routine histopathologic examination. These methods have been applied to LSCC in order to evaluate a range of potential prognostic indicators, including DNA ploidy, proliferative activity, and oncogene amplification.
EGFR is frequently and early overexpressed in LSCC, mainly by post-translational mechanisms. EGFR expression retains a strong predictive value independently of treatment (surgery, chemotherapy and radiation) and adversely influences overall relapse-free and metastasis-free survival in LSCC. At present, EGFR is the most reliable biological marker for molecular characterisation, aggressiveness and invasiveness of LSCC.
Alterations of p53 protein expression and mutations of the p53 gene have been proposed as independent predictors of recurrence in LSCC, however with controversial prognostic value.
p53 protein overexpression has been detected in a high percentage of LSCC correlating well with p53 gene mutation.
p53 gene mutation has been suggested more reliably than p53 protein overexpression for characterisation, predicting also the response to radiotherapy in LSCC patients. This observation is in accordance with the biological role of p53, which mediates apoptosis associated with DNA damage.
Alterations in p53 status have been evaluated in healthy mucosa, precancerous lesions and tumour cells in order to predict the development of LSCC and secondary primary tumours. Mutations of p53 have also been evaluated to detect whether multiple primary tumours have a mono- or polyclonal origin, without however, definitive conclusions.
In LSCC, degradation mediated by other cellular proteins, such as MDM2 or by human papillomavirus (HPV) E6 oncoprotein may represent alternative pathways leading to loss of p53 function.
A p53 gene therapy approach has already been shown to induce apoptosis, radio- and chemosensitisation in cell lines and this, in combination with radiotherapy or chemotherapy, is a rational possibility. Another potential application considered the treatment of dysplastic lesions, as p53 mutations seem to occur early in laryngeal carcinogenesis.
Telomerase activity often is present at high levels in most laryngeal cancer cells. It can at least partly depend on h-TERT gene (coding for catalytic subunit of telomerase) overexpression. It can be used for molecular epidemiology, diagnostics and targeting.
An early CCND1 overexpression is often detectable without evidence of gene amplification; it can be used for molecular epidemiology but it seems to retain a lower prognostic value, if compared with CCND1 amplification. The latter is a marker of aggressiveness and has an impact on relapse-free and overall survival in LSCC.
An overexpression of metalloproteases, hyaluronidases and cathepsin D is often detectable in tumour cells. These molecules are responsible for degradation of extracellular matrix and thus play an important role in tumour growth, invasion and metastasis, as well as in tumour-induced angiogenesis. In addition, overexpression of CD44 hyaluronan receptor in a less glycanated form is observed.
Among the extracellular matrix components, the proteoglycan versican appeares to be overexpressed becoming the macromolecule characteristic of the tumour state and being another marker of aggressiveness. Similarly, hyaluronan is found in increased amounts and of rather smaller molecular size. Alterations, also, in the sulphation pattern of chondroitin/dermatan sulphate are observed, indicating different expression of sulphotransferases.
Human papillomavirus (HPV) may affect epithelia with mucosal or epidermal tropism according to genotype. It has been reported that oncosuppressors such as p53 and pRb/RB1 are inhibited and degraded by HPV oncoproteins, while overexpression of oncogenes such as EGFR and cyclins A and B is induced.
Type II oestrogen binding sites (EBS), normally found in laryngeal mucosa, have been reported that may partly mediate tumour growth inhibition by tamoxifen and quercetin and could be possible targets for chemoprevention and therapy.
S100A2 has recently been described as an actual oncosuppressor with a prognostic significance stronger than simple histopathological grading. Its underexpression in cancer cells is inversely proportional to tumour differentiation.
Methyl-phydroxyphenyllactate esterase (MEPHLase) low activity in LSCC is associated with poor differentiation and shorter overall survival and metastasis-free survival.
Type 2 cyclo-oxygenase activity seems to promote tumour neoangiogenesis. However, evidence exists that low COX2 expression indicates poor differentiation and higher aggressiveness and invasiveness.
Galectin-3 participates in a variety of cell processes and mediating cell-to-cell interactions. Its expression seems positively associated with tumour keratinisation and histological grade and a significant correlation was described between galectin-3 tumour positivity and longer metastasis-free and overall survival in LSCC patients.
Nikolaos S Mastronikolis ; Theodoros A Papadas ; Panos D Goumas ; Irene-Eva Triantaphyllidou ; Dimitrios A Theocharis ; Nikoletta Papageorgakopoulou ; Demitrios H Vynios
Head and Neck: Laryngeal tumors: an overview
Atlas Genet Cytogenet Oncol Haematol. 2008-12-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview