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PubMed1998

p16/CDKN2 alterations and pRb expression in oesophageal squamous carcinoma.

BACKGROUND: Upregulation of the cell cycle associated genes, p16/CDKN2 and the retinoblastoma susceptibility gene (Rb), is commonly seen during the proliferation of normal cells. An inverse relation between the expression of p16/CDKN2 and Rb has been noted in many tumours, but has not yet been determined in oesophageal squamous carcinoma. AIMS: To investigate p16/CDKN2 genetic alterations and both the p16/CDKN2 and the Rb protein (pRb) immunophenotypes in oesophageal squamous carcinoma. METHODS: Twenty primary oesophageal squamous carcinomas were examined for mutations in p16/CDKN2 by the polymerase chain reaction, single stranded conformational polymorphism, and DNA sequencing. Synthesis of p16/CDKN2 and pRb proteins was determined by immunohistochemistry in 19 specimens of formalin fixed, paraffin wax embedded tissues. RESULTS: Mutations of p16/CDKN2 were not detected in exons 1 and 2. In only one case, G to C and C to T base changes were detected in a non-coding region of exon 3. Expression of p16/CDKN2 and Rb was observed in both normal and neoplastic areas of tissue sections, indicating neither consistent homozygous deletion nor consistent hypermethylation of the genes in tumours. Fourteen tumours showed an inverse expression of p16/CDKN2 and Rb. An increased percentage of cells that immunostained positively for p16/CDKN2 but not for pRb was observed in eight tumours, five of which had no detectable pRb, suggesting defective Rb expression in these oesophageal squamous carcinomas. CONCLUSIONS: These results indicate that p16/CDKN2 mutations occur infrequently in oesophageal squamous carcinoma. The alteration of the Rb gene is suggested as an important step in the development of these tumours.

Aged↗

PubMed1999

Mutational analysis of the PTEN/MMAC1 gene in primary oesophageal squamous cell carcinomas.

AIM: To investigate whether PTEN/MMAC1 mutations play a role in the carcinogenesis of oesophageal squamous cell carcinoma. METHODS: A panel of 33 primary oesophageal squamous cell carcinoma tumour samples and 20 corresponding morphologically normal tissues was examined for mutations in all nine exons of the PTEN/MMAC1 gene by means of polymerase chain reaction single strand conformational polymorphism analysis (PCR-SSCP) and direct DNA sequencing methods. RESULTS: Only one of 33 oesophageal squamous cell carcinomas showed an aberrant SSCP band. Further sequencing analysis of this sample revealed an 802 -29 T-->C substitution in intron 7. PTEN/MMAC1 mutations were not found in the mutational "hot spot" in exon 5, even after direct sequencing of six oesophageal squamous cell carcinoma samples and three normal tissues. However, a deletion of one nucleotide T at position 492 +8 in intron 5 was seen in all samples. CONCLUSION: These results suggest that PTEN/MMAC1 mutations do not play a major role in the carcinogenesis of oesophageal squamous cell carcinoma.

Aged↗

PubMed2004

Effect of human papillomavirus-16 infection on CD8+ T-cell recognition of a wild-type sequence p53264-272 peptide in patients with squamous cell carcinoma of the head and neck.

PURPOSE: Wild-type sequence (wt) p53 peptides are attractive candidates for broadly applicable cancer vaccines, currently considered primarily for patients whose tumors overexpress p53. Circumstances exist, however, where increased p53 degradation may result in appreciable presentation of p53-derived peptides, despite low p53 expression. Squamous cell carcinoma of the head and neck is associated with oncogenic human papillomavirus (HPV) subtypes, which inactivate p53 through proteasomal degradation. The criterion of p53 overexpression would exclude these individuals from wt p53-based immunotherapy. EXPERIMENTAL DESIGN: We tested the correlation of HPV infection with enhanced antigenicity of the p53 protein and postulated that removal of HPV-16(+) tumors with enhanced p53(264)-(272) peptide presentation might lead to a drop in T cells specific for this peptide in vivo. Circulating frequencies of T cells specific for the HLA A*0201:p53(264)-(272) complex were measured ex vivo using dimeric HLA:peptide complexes in 15 head and neck cancer patients before and 6 months after tumor excision. RESULTS: CD8+ T-cell recognition of HLA A*0201 restricted wt p53(264)-(272) peptide presented by HPV-16(-) squamous cell carcinoma of the head and neck lines was enhanced by HPV-16 E6 expression, sometimes exceeding that of a naturally transformed, HPV-16(+) wt p53 expressing squamous cell carcinoma of the head and neck cell line. In patients with HPV-16(-) tumors, the frequency of wt p53(264-272)-specific T cells remained largely unchanged after tumor removal. However, a significant decline in frequency of anti-p53(264-272) T cells was observed postoperatively in HPV-16(+) patients (P < 0.005). CONCLUSIONS: Recognition of HPV-associated squamous cell carcinoma of the head and neck appears associated with levels of wt p53-specific T cells and inversely with p53 expression. p53 peptides may be useful tumor antigens for squamous cell carcinoma of the head and neck immunotherapy in addition to viral gene products.

Aged↗

PubMed2005

Overexpression of the cytokine osteopontin identifies aggressive laryngeal squamous cell carcinomas and enhances carcinoma cell proliferation and invasiveness.

PURPOSE: Osteopontin is a secreted cytokine that binds to the cell surface CD44v6 receptor. We studied osteopontin and CD44v6 expression in laryngeal squamous cell carcinomas and correlated osteopontin expression levels with clinicopathologic tumor features. EXPERIMENTAL DESIGN: We used immunohistochemistry, immunoblotting, and reverse transcription-PCR to study osteopontin expression in 58 laryngeal squamous cell carcinomas. Cultured squamous carcinoma cells were treated with exogenous osteopontin or with RNA interference to knockdown osteopontin expression. RESULTS: Osteopontin expression was higher in all the invasive carcinomas than in patient-matched normal mucosa. Its expression levels were significantly correlated with tumor stage and grade and with the presence of lymph node and distant metastases. Osteopontin positivity was negatively correlated with overall survival (P = 0.03). Osteopontin expression was paralleled by intense cell surface reactivity for CD44v6. Treatment of squamous carcinoma cells with recombinant osteopontin sharply increased proliferation and Matrigel invasion in comparison with the untreated cells parallel to activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/mitogen-activated protein kinase signaling cascade. Osteopontin knockdown by RNA interference, anti-CD44 antibodies, and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibition prevented these effects. CONCLUSIONS: These results identify osteopontin as a marker and a potential therapeutic target in cases of aggressive laryngeal squamous cell carcinomas.

Adult↗

PubMed1998

Factors regulating SCC antigen expression in squamous cell carcinoma of the uterine cervix.

Expression of squamous cell carcinoma (SCC) antigen emerged concurrently with squamous formation of the uterine cervix and increased during the neoplastic transformation of the cervical squamous epithelium. SCC antigen expression differed considerably among the histomorphologic cell types of cervical carcinoma. Large cell nonkeratinizing carcinoma contained high levels of the antigen. In contrast, no appreciable expression of SCC antigen was observed in small cell nonkeratinizing carcinoma. The pattern of SCC antigen expression closely coincided with EGF receptor (EGF-R) expression in cervical squamous neoplasia. This suggests that the expression of SCC and EGF-R in cervical carcinoma is related to the differentiation or dedifferentiation processes of the tumor cells. SCC production by CaSki cervical epidermoid carcinoma cells was stimulated by EGF. It seems likely that an autocrine system, in which EGF serves as the signal, may exist in cervical squamous carcinoma. 17beta-estradiol and L-triiodothyronine were found to upregulate EGF-R expression, proliferative potential and SCC production in the CaSki cervical carcinoma cells.

Antigens, Neoplasm↗

PubMedDate not supplied

High levels of cytokeratin 19 fragments but no evidence of cytokeratins 1, 2, 10/11, 14 or filaggrin in the serum of squamous cell lung carcinoma patients.

The CYFRA 21-1 assay detects circulating fragments of cytokeratin 19, which is a sensitive marker for the diagnosis of lung cancers, particularly squamous cell carcinomas and adenocarcinomas. Epidermis-type proteins, such as cytokeratins 1, 2, 10/11 and 14 or filaggrin, are also expressed in squamous cell carcinomas. These could also be pertinent tumor markers, ideally as sensitive as CYFRA 21-1 and more specific for squamous cell lung cancer. To verify this hypothesis, using monoclonal antibodies produced in our laboratory, we developed immunoassays specific for these proteins. After optimization, the immunoassays were evaluated in sera from 91 controls and 138 patients with squamous cell lung cancer and compared to conventional tumor markers (CEA, SCC Ag and CYFRA 21-1). Less than 14% of the sera were above the lower limit of detection of the cytokeratin- and filaggrin-specific immunoassays. Moreover, part of these positive sera were induced by the presence of interfering heterophilic antibodies in sera. Thus, in patients with squamous cell lung cancer, we confirmed the high diagnostic sensitivity of CYFRA 21-1 (55.6%) but were unable to detect significant levels of epidermis-type cytokeratins or filaggrin.

Antibodies, Monoclonal↗

PubMed2001

Collision of squamous-cell carcinoma with melanoma in situ in a child with xeroderma pigmentosum.

Coexistence (collision) of two different neoplasms in the same lesion has previously been documented by several authors. In this report, we describe a 13-year-old boy with xeroderma pigmentosum presenting with squamous-cell carcinoma and melanoma arising at the same site on the nose. Histopathologically, the melanoma component of the lesion was located mainly eccentrically to the squamous-cell carcinoma component. Immunohistochemical stains confirmed the histopathologic findings. Mutations for p53 assessed using single-strand conformation polymorphism, and sequencing analysis revealed a CC-to-TT transition at codon 159 of the p53 gene in the squamous-cell component but not in the melanoma component. This finding suggests a possible role for UV in the pathogenesis of at least the squamous-cell component of the tumor. To the best of our knowledge, this is the first report of a collision tumor comprising squamous-cell carcinoma and melanoma arising in childhood.

Adolescent↗

PubMed2004

E-cadherin, CD44 and CD44v6 in squamous intraepithelial lesions and invasive carcinomas of the uterine cervix: an immunohistochemical study.

OBJECTIVE: To evaluate the immunoexpression pattern of E-cadherin, CD44std and the variant isoform v6 in normal squamous epithelium, low and high squamous intraepithelial lesions (SILs) and invasive squamous cell carcinomas (ISCCs) of the uterine cervix. The purpose was to determine whether any distinctive change in antigenic expression could contribute to the recognition of the earliest commitment to neoplasia and/or the onset of the invasive phenotype. METHODS: Immunohistochemistry using the avidin-biotin indirect immunoperoxidase method was used to study the protein expression of epithelial cadherin (E-cadherin), cluster differentiation 44 (CD44), and the isoform v6 (CD44v6) in 124 human cervical samples (5 normal, 39 low-grade, 54 high-grade and 26 ISCCS) in formalin-fixed, paraffin-embedded tissue blocks. RESULTS: Membranous expression of E-cadherin, CD44 and CD44v6 was preserved in normal squamous epithelium and in low-grade squamous intraepithelial lesions. A significant association was observed with the histological grade of the SILs and the immunoreactivity (membranous versus cytoplasmic) pattern of E-cadherin (p < 0.001), CD44std (p = 0.027) and CD44v6 (p < 0.001). A loss of membranous staining and a progressive increase in cytoplasmic staining was observed from low to high grade SILs to ISCCs. CONCLUSIONS: Our study demonstrates that during the development of cervical lesions substantial qualitative (subcellular localization-membrane to cytoplasmic) and quantitative alterations (changes in expression) occur in the protein expression of E-cadherin, CD44, and CD44v6 in cervical cancer. The most striking observation was the decrease in membranous immunoreactivity and the progressive increase in cytoplasmic staining of E-cadherin, CD44 and CD44v6, relating to loss of differentiation as a consequence of neoplastic transformation.

Biomarkers, Tumor↗

PubMed2005

Enhanced expression of Aggrus (T1alpha/podoplanin), a platelet-aggregation-inducing factor in lung squamous cell carcinoma.

Aggrus (T1alpha/podoplanin, known as a specific marker for type I alveolar cells or lymphatic endothelial cells) is a transmembrane sialoglycoprotein that aggregates platelets. Previously, we showed that upregulated expression of Aggrus occurs in colorectal tumors or testicular tumors and could be associated with platelet-aggregating activity and metastatic ability. In testicular tumors, Aggrus is specifically expressed in seminoma. The present study investigates Aggrus expression in human primary lung cancer tissues of different types. Microarray analysis demonstrated that aggrus was significantly expressed in squamous cell carcinoma (10/15; 66.7%). Immunohistochemical analysis also showed that the incidence of positive staining in sections of squamous cell carcinoma (7/8; 87.5%) was higher than that in adenocarcinoma (2/13; 15.4%). Furthermore, Aggrus expression was detected in a squamous cell carcinoma cell line, NCI-H226, by real-time PCR. These findings indicated that overexpression of Aggrus occurred in squamous cell carcinoma of the lung. Therefore, Aggrus could be a useful diagnostic marker for squamous cell carcinoma of the lung.

Biomarkers, Tumor↗

PubMed1993

Early squamous lung cancer and longer survival rates.

The criteria for early squamous lung cancer remain open to discussion as patients who have been treated for early stage lung cancer, such as T1N0M0, and appear to have been cured clinically may die from recurrent or metastatic tumors. We reviewed the pathological data on 242 surgical patients with squamous lung cancer and found 31 cases (13%) of early lung cancer, included were early lung cancer of the hilar type as a lesion restricted to the bronchial wall without lymph node involvement, and early lung cancer of the peripheral type as a lesion of less than 2 cm and surrounded by visceral pleura but without lymph node involvement. Of 89 patients with hilar-type squamous lung cancer, 17 (19%) had early lung cancer, and 14 (9%) of 153 patients with peripheral-type squamous lung cancer had early lung cancer (p < 0.05). For early lung cancer of the hilar type, all but 1 (94%) were detected using sputum cytologic study and bronchoscopy. For early lung cancer of the peripheral type, all were detected on chest X-ray, but 57% were cytologically proven to be malignant. The 5-year survival rate for patients with early lung cancer, according to this new criteria is 90%; 92% for the hilar type and 88% for the peripheral type. Thus, classification of early squamous lung cancer is pertinent for determining the prognosis and selection of treatment. We emphasize that efforts be made to detect early lung cancer.

Adult↗

PubMed1991

Different behaviors in the production and release of SCC antigen in squamous-cell carcinoma.

Squamous-cell carcinoma antigen (SCC antigen), formerly referred to as TA-4, is closely related to the grade of differentiation. Immunohistochemical studies have demonstrated that SCC antigen is also increased in the keratinizing or large-cell nonkeratinizing type of squamous-cell carcinoma but not in the small cell type. On the other hand, the appearance rate of SCC antigen in the blood circulation is almost the same in these three types of squamous-cell carcinoma. The present study was conducted to clarify the discrepancy in the production and release of this tumor marker using a squamous-cell carcinoma cell line, SKG-IIIa. SKG-IIIa cells were treated with 10 microM 5-azacytidine, a potent hypomethylating agent, to obtain several sublines with different behavior in the production of SCC antigen, and cloned by a limiting dilution technique. One subline (B-5) released significantly greater amounts of SCC antigen into the incubation medium as compared with other sublines (A-5). In in vivo studies, groups of nude mice received subcutaneous injections of the A-5 or B-5 subline, and the serum SCC antigen levels were determined after the animals exhibited palpable tumors. The serum levels of SCC antigen were significantly higher in the animals inoculated with the B-5 cells than in those inoculated with the A-5 cells. On the other hand, flow-cytometric analysis and immunohistochemical studies using a polyclonal antibody revealed that the intracellular contents of SCC antigen were greater in the A-5 cells than in the B-5 cells. Radioautography was performed using a 125I-labeled monoclonal antibody specific against the acidic fraction of this marker, a dominant form released outside the cells, which revealed that the production of the acidic fraction was somewhat greater in the B-5 cells than in the A-5 cells. These results suggest that the production and release of SCC antigen are different phenomena in squamous-cell carcinoma and that the release of SCC antigen is likely influenced by the production of the acidic fraction.

Animals↗

PubMed1993

'Anti-metastatic' nm23 gene product expression in keratoacanthoma and squamous cell carcinoma.

An inverse correlation has been demonstrated between nm23 gene expression and metastasis. The gene is located on chromosome 17q (q1.1-q2.1), a region distinct from tumour suppressor gene p53. We have previously reported expression of mutant products of p53 gene to be significantly associated with worsening degrees of differentiation in squamous cell carcinoma. nm23 gene product, which shows complete identity to human erythrocyte nucleoside diphosphate kinase, was used to raise an affinity-purified polyclonal antibody Ab-11 which is applicable to formalin-fixed and paraffin-embedded tissues. Keratoacanthomas and squamous cell carcinomas of the epidermis form a fascinating human tumour model in which to test the hypothesis that the nm23 gene confers 'anti-metastatic' properties, since the former never metastasise while the latter have this potential. Two observers rated immunohistochemistry for the nm23 gene product as the proportion of tumour positive from grades 1-4 (corresponding to 25, 50, 75 and 100% of tumour cells stained). Nineteen typical keratoacanthomas, 20 well, 21 moderately and 8 poorly differentiated epidermal squamous cell carcinomas were studied. The Jonckheere-Terpstra test statistic of association between staining grade and lesion type was 762.5, p = 0.189 (2 tails), p = 0.0945 (1 tail). There was no statistically significant trend in tumour staining from keratoacanthoma through decreasing grades of differentiation of squamous cell carcinoma. nm23 product expression does not appear to correlate with differentiation, itself an indicator of metastatic potential, in this system of human squamous cell neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Acetic acid recovery of gynecologic liquid-based samples of apparent low squamous cellularity.

OBJECTIVE: To characterize cervicovaginal cytology samples with < 5,000 squamous cells on the initial ThinPrep slide (Cytyc Corp., Boxborough, Massachusetts, U.S.A) and to attempt sample recovery using acetic acid. STUDY DESIGN: Cervicovaginal cytology samples with <5,000 squamous cells on the original ThinPrep slide and residuum were reprocessed by adding 3 mL of 3:1 CytoLyt (Cytyc)/glacial acetic acid with production of a second slide. Both slides were reviewed for squamous cell quantitation and the presence of background material and abnormal cells. RESULTS: From a total of 1,833 cases, 147 (8.0%) were identified for reprocessing; 71 (48.3%) were grossly bloody and 58 (39.4%) grossly cloudy. Reprocessing resulted in a second slide with > 5,000 squamous cells in 116 (78.9%) cases and was most effective on cloudy samples (89.7% recovery) and bloody samples (71.8% recovery). Abnormal cells were identified in 13 (8.9%) reprocessed samples. In all but 2 cases the abnormal cells were present on the initial slide and demonstrated the same degree of abnormality as the reprocessed slide but were fewer in number. CONCLUSION: Acetic acid recovery increases squamous cell recovery when initially inadequate, reducing the number of unsatisfactory cases and in rare cases identifying a cytologically significant lesion not apparent on the original slide.

Acetic Acid↗

PubMedDate not supplied

Metastatic laryngeal basaloid squamous cell carcinoma simulating primary small cell carcinoma of the lung on fine needle aspiration lung biopsy. A case report.

BACKGROUND: First described in 1986, the basaloid squamous variant of laryngeal carcinoma is an uncommon, aggressive neoplasm with early presentation of metastatic disease and widespread dissemination. It is characterized primarily by its biphasic morphologic appearance. CASE: A 64-year-old female smoker presented with left hilar and right lower lung lobe masses. The fine needle aspiration cytologic findings were consistent with features of primary undifferentiated small cell carcinoma. CONCLUSION: The basaloid squamous cell carcinoma of head and neck region is a highly malignant neoplasm with frequent metastatic disease at the time of diagnosis. Metastatic deposits may consist of basaloid and/or squamous carcinoma cells. The basaloid component of this biphasic neoplasm is poorly differentiated and demonstrates cytologic features that mimic undifferentiated small cell carcinoma. Previous reports of cervical lymph node metastases from basaloid squamous carcinoma indicate frequent misdiagnosis as small cell carcinoma. Pulmonary metastases are more problematic since they introduce the possibility of a second primary lesion in these patients who have a frequent history of cigarette and/or ethanol abuse. Immunohistochemistry is useful in the distinction of metastatic basaloid squamous carcinoma from a second primary cell carcinoma of the lung.

Biomarkers, Tumor↗

PubMed2001

Mucins as differentiation markers in bronchial epithelium. Squamous cell carcinoma and adenocarcinoma display similar expression patterns.

UNLABELLED: Highly glycosylated apomucins are important to maintain the viscoelastic properties of the mucus. Changes in their expression are frequently associated with inflammatory and neoplastic conditions. We analyzed the expression of apomucins in normal respiratory tract (n = 8) and compared it with distal, peritumoral, and tumoral epithelia from patients with squamous cell carcinoma (n = 20), adenocarcinoma (n = 13), and small cell carcinoma (n = 12). Squamous metaplasia (n = 16) was also analyzed. MUC1, MUC2, MUC4, MUC5AC, MUC6, and MUC8 apomucins were detected by immunohistochemistry, and mucin transcripts by in situ hybridization and reverse transcriptase polymerase chain reaction. Bronchial epithelium from normal individuals and distal epithelium from cancer patients showed a similar expression pattern: MUC1, MUC4, and MUC8 were always present, MUC2 and MUC5AC showed more variability, and MUC6 was focally detected. MUC5AC was downregulated in peritumoral epithelium and in squamous metaplasia, and MUC6 was upregulated in peritumoral epithelium. A reduced expression of MUC4, MUC5AC, and MUC8 was observed in non-small cell carcinomas, regardless of their histologic subtype. In small cell tumors, only MUC1 was consistently expressed. CONCLUSIONS: (1) peritumoral epithelium and squamous metaplasia show an abnormal pattern of mucin expression; (2) squamous cell carcinomas and adenocarcinomas display a similar pattern of mucin gene expression, supporting the concept of a common cellular origin.

Adenocarcinoma↗

PubMed1990

Inverted papillomas and associated squamous cell carcinomas.

Inverted papillomas of the nose and paranasal sinuses are found to be associated with squamous cell carcinomas in a small percentage of cases. The records of forty-six patients treated for inverted papillomas in these areas over a 10-year period were reviewed. Eleven patients (24%) were found to have squamous cell carcinoma, and one carcinoma in situ, in relationship to the inverted papillomas. This is a much higher percentage than generally reported. Four of these patients were found to have inverted papillomas coincidentally in surgical specimens resected for squamous cell carcinoma. Patients with squamous cell carcinoma were found to be in older age groups, were more likely to manifest epistaxis than the more common unilateral nasal obstructive symptoms, and had less time between the onset of symptoms and presentation than those with inverted papillomas alone. The clinical presentation, treatment, and outcome of inverted papillomas and squamous cell carcinomas in association with inverted papillomas are discussed.

Adult↗

PubMedDate not supplied

Contralateral parotid-sparing radiotherapy in patients with unilateral squamous cell carcinoma of the head and neck: technical methodology and preliminary results.

AIMS AND BACKGROUND: Radiation-induced permanent xerostomia occurs frequently in patients affected by squamous cell carcinoma of the head and neck treated by parallel opposed lateral fields. An ipsilateral technique by using co-planar multiple-field arrangement was designed to restrict treatment to the primary tumor and neck on the same side for patients with selected lateralized squamous cell carcinoma of the head and neck. METHODS: From November 2001 till December 2002, 30 patients affected by squamous cell carcinoma of tonsillar fossa, retromolar trigone, alveolar ridge and oropharyngeal lateral wall were included in this investigational trial and treated with an ipsilateral multiple field technique: in detail, oblique opposed two upper half fields were planned ipsilaterally to the squamous cell carcinoma site to cover PTV1 and PTV2, whereas an anterior-lower half field was planned to encompass the lower neck node area above clavicles. On CT scans, the contralateral parotid gland was outlined as organ at risk and the contralateral upper lymph node area was contoured as volume of interest. In selected cases, convergent oblique two wedge-pair half fields were added to opposed oblique two-field technique in order to cover only PTV2: generally, in these patients, PTV1 received 1.8 Gy per fraction and PTV2 2.2 Gy per fraction up to total doses of 54 Gy and 66 Gy, respectively. RESULTS: Ten patients received radical radiotherapy, 9 patients radical alternating chemo-radiotherapy, and 11 patients adjuvant radiotherapy. At the end of treatment, unilateral confluent mucositis was recorded in 13 (43%) patients and unilateral moist skin epidermolysis in 14 (46%) patients. Six months after the end of radiotherapy, grade 0 xerostomia was recorded in 20 (67%) patients. No patient experienced grade 2+ xerostomia. At a median follow-up of 12 months, 26 (86%) patients were alive and well; 2 patients (6%) developed contralateral neck node failure, both 4 months after the end of ipsilateral radiotherapy. CONCLUSIONS: These results, although preliminary, suggest that by using an ipsilateral radiotherapy technique, symptomatic xerostomia may be avoided in selected patients with lateralized squamous cell carcinoma of the head and neck without an increased short-term risk of contralateral nodal failure.

Aged↗

PubMed2004

Squamous cell carcinoma related oncogene regulates angiogenesis through vascular endothelial growth factor-A.

BACKGROUND: Squamous cell carcinoma related oncogene expression (SCCRO) correlates with vascular endothelial growth factor-A expression. This data is validated in human lung tumors and provides a putative pathway for angiogenesis in a subset of squamous cell carcinomas. Squamous cell carcinoma related oncogene is a novel oncogene identified by positional cloning of a recurrent amplification at 3q26.3. It is over-expressed in 39.8% of lung, head and neck, cervical, and ovarian carcinomas. SCCRO imparts an aggressive phenotype to affected cancers, which may be related to increased angiogenesis due to SCCRO expression. Our previous work has demonstrated a link between SCCRO and vascular endothelial growth factor-A (VEGF-A) expression in vitro, suggesting a mechanism for SCCRO-induced angiogenesis. The present study aims to confirm and validate this link between SCCRO and VEGF-A expression in an ex vivo human tumor cohort. METHODS: Fresh tissue was collected at Memorial Sloan-Kettering Cancer Center from 34 patients undergoing primary resection of lung squamous cell carcinomas. RNA was extracted from this tissue, reverse-transcribed, and real-time polymerase chain reaction (RT-PCR) was carried out using a BioRad iQ iCycler with SYBR green fluorophore. Microvessel counting was performed on the tumor specimens using CD34 immunohistochemistry. RESULTS: The expression of both SCCRO and VEGF-A mRNA varies widely in both tumor and normal tissue. SCCRO and VEGF-A co-expression was significantly correlated (R(2) = 0.63; P < 0.032). Microvessel counts were not associated with expression of SCCRO or VEGF-A and failed to significantly predict survival. VEGF-A expression in this patient group is a predictor of overall survival (P < 0.032). CONCLUSIONS: VEGF-A expression correlates with SCCRO expression in these primary human lung squamous cell carcinomas and is a predictor of clinical behavior. This data supports the association of SCRRO and VEGF-A in the induction of angiogenesis.

Aged↗