Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma.

Human papillomaviruses (HPV) are associated with a subset of head and neck squamous cell carcinoma (HNSCC), particularly HPV16. This study analyzed the presence and genotype of high risk HPVs, viral DNA load and transcription of the E6/E7 mRNAs, in 231 consecutive HNSCC. Twelve out of 30 HPV16 DNA-positive tumors displayed high E6/E7 mRNAs levels and were localized in the oropharyngeal region.

CTIP2 expression in human head and neck squamous cell carcinoma is linked to poorly differentiated tumor status.

Background: We have demonstrated earlier that CTIP2 is highly expressed in mouse skin during embryogenesis and in adulthood. CTIP2 mutant mice die at birth with epidermal differentiation defects and a compromised epidermal permeability barrier suggesting its role in skin development and/or homeostasis. CTIP2 has also been suggested to function as tumor suppressor in cells, and several reports have described a link between chromosomal rearrangements of CTIP2 and human T cell acute lymphoblast leukemia (T-ALL).

Prediction of future metastasis and molecular characterization of head and neck squamous-cell carcinoma based on transcriptome and genome analysis by microarrays.

Propensity for subsequent distant metastasis in head and neck squamous-cell carcinoma (HNSCC) was analysed using 186 primary tumours from patients initially treated by surgery that developed (M) or did not develop (NM) metastases as the first recurrent event. Transcriptome (Affymetrix HGU133_Plus2, QRT-PCR) and array-comparative genomic hybridization data were collected. Non-supervised hierarchical clustering based on Affymetrix data distinguished tumours differing in pathological differentiation, and identified associated functional changes.

Cyclin L1 (CCNL1) gene alterations in human head and neck squamous cell carcinoma.

We evaluated the expression and amplification of cyclin L1 (CCNL1) gene, a potential oncogene localised in the commonly amplified 3q25-28 region, in human head and neck squamous cell carcinomas (HNSCCs). Overexpression was observed in 55 out of 96 cases (57%) and amplification in nine out of 35 tumours (26%) with no relationships to the clinico-pathological parameters. The Cyclin L1 antibody we developed labels nuclear speckles in tumour cells compatible with a role for CCNL1 in RNA splicing.

Analysis of a novel human gene, LOC92912, over-expressed in hypopharyngeal tumours.

We have identified by differential display a number of novel genes that are expressed in hypopharyngeal head and neck squamous cell carcinoma. We report here the characterisation of one of these novel human genes, LOC92912, that encodes a protein of 375 amino acids. The protein contains a RWD domain, a coiled-coil, and an E2 ubiquitin conjugating enzyme domain.

Head and neck squamous cell carcinoma transcriptome analysis by comprehensive validated differential display.

Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples.

Cisplatin-induced genes as potential markers for thyroid cancer.

Despite the uncontested role of p53 in cycle arrest/cell death after cisplatin treatment, to date the question whether wild-type p53 confers a resistant or sensitive status on the cell is still a matter of debate. Isogenic and isophenotypic human thyroid papillary carcinoma cell line variants for p53 differently expressed cycle genes after cisplatin treatment. Seven genes (CDC6-related protein, CCNC, GAS1, TFDP2, MAPK10/JNK3, WEE1, RPA1) selected after expression on an Atlas human cell cycle array were analyzed by quantitative real-time PCR.

Loss of HOP tumour suppressor expression in head and neck squamous cell carcinoma.

We report that homeodomain-only protein (HOP) is expressed in the suprabasal layer of normal upper aerodigestive tract epithelium and expression strongly decreases in hypopharyngeal carcinoma. Interestingly, HOP has very recently been shown to be a tumour suppressor involved in differentiation, suggesting that HOP may have a similar role in head and neck squamous cell carcinoma (HNSSC).

Wild-type p53 gene transfer into mutated p53 HT29 cells improves sensitivity to photodynamic therapy via induction of apoptosis.

Photodynamic therapy (PDT) is an effective local cancer treatment that induces cytotoxicity through the intracellular generation of reactive oxygen species. It is generally thought that p53 regulates chemotherapy and radiation therapy responsiveness via apoptosis induction control. The current study investigated whether cellular sensitivity to PDT is increased when a wild-type (wt) p53 status is restored by gene transfer in the established HT9blk Ala273-mutant p53 human colon cancer cell line.

Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.

The aim of this study was to evaluate the predictive value of five different biological factors in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy: (1) tumour grade scored according to the Elston-Ellis classification, (2) hormonal receptor (HR) status; (3) tumour cell proliferation evaluated by Ki-67 staining, (4) HER-2 and topoisomerase II alpha (TopoIIalpha) expression evaluated by immunohistochemistry (IHC), (5) HER-2 and TopoIIalpha amplification evaluated by real-time polymerase chain reaction (PCR). 119 patients with operable breast cancer were treated with six cycles of FEC (100 5-fluorouracil (5-FU) 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2). Tumour response was assessed clinically and by computed tomography (CT) scan, then by pathological assessment.

Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world. There is a need, for both clinical and scientific reasons, to find markers to identify patients with aggressive disease as early as possible, and to understand the events leading to malignant transformation and susceptibility to metastasis. We report the first large-scale gene expression analysis of a unique HNSCC location, the hypopharynx.

Differential expression profiling of head and neck squamous cell carcinoma (HNSCC).

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a large-scale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients.

Loss of MDM2 expression in human head and neck squamous cell carcinomas and clinical significance.

The transforming potential of the MDM2 oncogene has been attributed to the overproduction of the protein. In order to investigate regulation of MDM2 expression in head and neck squamous cell carcinomas, we analysed MDM2 gene amplification, and mRNA and protein expression in tumour specimens from 62 patients, in cell lines, and in normal epithelium adjacent to tumours or obtained from healthy patients. Additionally, TP53-induced MDM2-P2 transcription was evaluated and compared with TP53 status.

G3BP is overexpressed in human tumors and promotes S phase entry.

The expression of the human Ras-GTPase activating protein (GAP)-binding protein (G3BP) was studied in human tumors and cell lines of different origins. Northern blot analysis and immunoblotting experiments showed enhanced expression of G3BP in all tumor samples as compared to healthy tissue. The enhanced expression does not seem to be related to the tumor site or to the stage of development of the cancer.

Bcl-2/Bax protein ratio predicts 5-fluorouracil sensitivity independently of p53 status.

p53 tumour-suppressor gene is involved in cell growth control, arrest and apoptosis. Nevertheless cell cycle arrest and apoptosis induction can be observed in p53-defective cells after exposure to DNA-damaging agents such as 5-fluorouracil (5-FU) suggesting the importance of alternative pathways via p53-independent mechanisms. In order to establish relationship between p53 status, cell cycle arrest, Bcl-2/Bax regulation and 5-FU sensitivity, we examined p53 mRNA and protein expression and p53 protein functionality in wild-type (wt) and mutant (mt) p53 cell lines.

Detection of prostate-specific antigen- or prostate-specific membrane antigen-positive circulating cells in prostatic cancer patients: clinical implications.

Objectives: To evaluate the clinical benefit from using circulating prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) mRNA detection in prostate cancer staging and in follow-up.

Methods: Nested reverse transcriptase-polymerase chain reaction (RT-PCR) assays were performed on RNA extracted from blood drawn from 56 patients with prostate cancer before any treatment. Additionally, assays were done on posttreatment samples from 50 patients who were followed up by serum PSA level, to determine whether any relationship exists between RT-PCR results and tumor recurrence.

[Long-term prognostic role of steroid receptors in cancer of the breast].

We screened for the prognostic value of estrogen receptor (ER) and progesterone receptor (PR) through a multicentric study of 2,257 operable breast cancer patients who did not received adjuvant therapy. Three hundred and seven local-regional recurrences, 105 metachronous contralateral breast cancer, 589 metastases and 537 deaths from cancer had been diagnosed with a median follow-up of 8.5 years.

Amplification of 11q13 DNA markers in head and neck squamous cell carcinomas: correlation with clinical outcome.

This study was performed on 282 patients with primary head and neck squamous cell carcinomas to evaluate the prognostic importance of 11q13 amplification. Amplification of the 11q13 DNA markers, HST-1/FGF-4 and BCL-1, evaluated by Southern and slot blot hybridisation, was detected in 52% of tumours. 11q13 amplification was associated with tumour site since this alteration occurred in 76% of tumours arising in the hypopharynx, versus 40% in the other sites (P = 0.

Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers.

The prognostic value of oestrogen receptor (ER) and progesterone receptor (PR) was estimated through a multicentric study of 2257 operable breast cancer patients followed up for a median of 8.5 years. None of the patients had received adjuvant therapy.

Alteration of the C-met oncogene locus in human head and neck-carcinoma.

The c-met proto-oncogene encodes the receptor for the hepatocyte growth factor/scatter factor (HGF/SF) which induces eel proliferation and motility. We have analysed the genetic alteration involving the c-met locus on chromosome 7q31 using the pMet H polymorphic probe, in tumor and normal DNA from 87 patients with head and neck squamous cell carcinomas (HNSCC). We report the observation of loss of heterozygosity (LOH) at this locus in 23% of informative cases, contrasting with the previously reported 40% LOH detected in breast cancer.

Rflp analysis of the L-myc oncogene in head and neck-cancer - relationship study with susceptibility and disease progression.

The L-myc DNA restriction fragment length polymorphism (RFLF), revealed by EcoRI digestion, has been evaluated in a case-control study including 161 head and neck cancer (HNSCC) patients and 160 normal healthy individuals with similar smoking and alcohol habits. No significant difference in the distribution of L-myc genotypes (LL, LS or SS) was found between the two populations implying thus no predisposition to head and neck tumour by either allele. There was no significant association between L-myc genotypes and the usual clinicopathological features such as T staging, differentiation status and lymph node involvement.

Frequent amplification of 11q13 DNA markers is associated with lymph node involvement in human head and neck squamous cell carcinomas.

Amplification of 11q13 DNA markers, particularly hst-1/FGF4 oncogene and the bcl-1 locus, was evaluated in 178 head and neck squamous cell carcinomas (SCCs) by Southern blot and slot blot hybridisation. Coamplification of hst-1/FGF4 and bcl-1 genes was found in 57% of primary tumours and in 60% of the 89 metastatic lymph nodes tested. The pattern of amplification was significantly similar in matched sets of primary SCCs and metastatic lymph nodes.

Influence of mastectomy techniques on estrogen and progesterone receptor analysis in carcinoma of the breast.

Gradual tumor tissue devascularization during mastectomy is thought to decrease estrogen (ER) and progesterone (PgR) receptor activity. To determine whether or not hormone receptor values could be influenced by different mastectomy techniques, 62 patients with carcinoma of the breast had a Tru-cut needle (Baxter Healthcare Corporation) biopsy (premastectomy sample) and underwent modified radical mastectomy (postmastectomy sample) either before (group 1, 40 patients) or after (group 2, 22 patients) axillary lymph node dissection. When the two surgical procedures were compared in 33 patients in whom it could be assessed, no significant tendency (p = 0.

Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas.

Matrix metalloproteinases are believed to play an important role in tumor invasion and metastasis. To examine the expression of the stromelysin 3 (ST3) gene, a new member of the matrix metalloproteinase gene family, 111 head and neck squamous cell carcinomas and 21 metastatic lymph nodes were analyzed by Northern blot. ST3 gene expression was observed in 106 carcinomas and 19 metastatic nodes, but in only 2 of 60 samples of corresponding normal tissue tested in parallel.

Expression of collagenase-related metalloproteinase genes in human lung or head and neck tumours.

We address the question as to whether increased metalloproteinase production might be related to the high regional recurrence rate of some carcinomas, and particularly head and neck squamous-cell carcinomas (SCC). Northern blot of total RNA prepared from 26 lung carcinomas, 107 head and neck carcinoma samples and corresponding normal tissue samples demonstrates the frequent and sometimes concomitant over-expression of the 2 stromelysin genes, the type-I collagenase gene and the pump-I gene in the head and neck tumour tissue samples. In these SCC, over-expression of the 2 stromelysin genes and the type-I collagenase gene (but not the pump-I gene) is associated with a high degree of tumour differentiation.