Series Of Squamous Cell Carcinomas Research Articles

External Auditory Canal Mass: A Case Series of Squamous Cell Carcinoma

Introduction: Squamous cell carcinoma of the temporal bone is extremely rare comprising 0.2% of all tumors of head and neck. Symptoms are nonspecific and may be mistaken for other more benign conditions as otitis, cholesteatoma and polyp. Hence, this condition may present as a diagnostic challenge. Case Discussion: We describe a case series of three patients who presented with external auditory canal (EAC) mass. The most common signs and symptoms are pruritus, decreased hearing and yellowish discharge. They were initially treated with otic antibiotics which afforded no relief. The first case is a 51 year-old female who underwent wide excision of the right ear canal and middle ear mass and right temporal craniotomy. Histopathology showed moderately differentiated squamous cell carcinoma with temporal tumor and subdural extension consistent with metastasis. The second case is a 53 year-old male who refused surgical management. He was non-compliant with work-up and follow-up and later on presented with left facial asymmetry and headache. CT scan showed a left inner and middle ear canal mass with extension to the auditory canal and protrusion into the left cerebellar hemisphere. Punch biopsy of the left EAC mass was done and pathologic report showed well-differentiated squamous cell carcinoma. Lastly, a 54 year old male who underwent Radical mastoidectomy with histopathology reports of a moderately differentiated squamous cell carcinoma. Conclusion: Standard treatment modality is still unclear because of the rarity of this condition. However, surgical resection with negative margins followed by concurrent chemotherapy and radiation is the most commonly performed approach1. For the above-mentioned patients, concurrent chemotherapy and radiation therapy was given which showed significant treatment response.

Detection of Equine Papillomaviruses and Gamma-Herpesviruses in Equine Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) seriously compromises the health and welfare of affected horses. Although robust evidence points to equine papillomavirus type 2 (EcPV2) causing genital lesions, the etiopathogenesis of equine SCC is still poorly understood. We screened a series of SCCs from the head-and-neck (HN), (peri-)ocular and genital region, and site-matched controls for the presence of EcPV2-5 and herpesvirus DNA using type-specific EcPV PCR, and consensus nested herpesvirus PCR followed by sequencing. EcPV2 DNA was detected in 45.5% of HN lesions, 8.3% of (peri-)ocular SCCs, and 100% of genital tumors, whilst control samples from tumor-free horses except one tested EcPV-negative. Two HNSCCs harbored EcPV5, and an ocular lesion EcPV4 DNA. Herpesvirus DNA was detected in 63.6%, 66.6%, 47.2%, and 14.2% of horses with HN, ocular, penile, and vulvar SCCs, respectively, and mainly identified as equine herpesvirus 2 (EHV2), 5 (EHV5) or asinine herpesvirus 5 (AsHV5) DNA. In the tumor-free control group, 9.6% of oral secretions, 46.6% of ocular swabs, 47% of penile samples, and 14.2% of vaginal swabs scored positive for these herpesvirus types. This work further highlights the role of EcPV2 as an oncovirus and is the first to provide information on the prevalence of (gamma-)herpesviruses in equine SCCs.

Keratin 36, a specific marker of tongue filiform papillae, is downregulated in squamous cell carcinoma of the mobile tongue.

Human keratin 36 (K36) is a member of the hair keratin family and is a marker of hair cortex differentiation. The human KRT36 gene is located on the long arm of chromosome 17 and belongs to the cluster of structurally unrelated acidic hair keratins. Recently, it has been reported that KRT36 mRNA is specifically expressed in normal tongue epithelium and downregulated in squamous cell carcinomas of the mobile tongue. Furthermore, KRT36 levels have been reported to be downregulated in clinically normal mobile tongue tissue that is adjacent to tumours, suggesting it could be a marker of pre-neoplastic changes. However, the exact role and the potential role of K36 in tongue tumour formation remains unclear. The aim of the present study was to investigate expression of K36 in a series of squamous cell carcinomas of the mobile tongue, normal mobile tongue and a small panel of other human tissues (normal tissue from the appendix, cervix, hair, lip, mamilla, nail, oesophagus, skin, thymus and vagina) and selected cancer tissue (cervical cancer, melanoma and basal cell carcinoma). Affinity purified polyclonal antibodies against K36 were generated and used for immunohistochemical analysis. The results revealed that in the normal tongue, K36 was detected specifically in the filiform papillae of the dorsal surface of the tongue. Additionally, none of the tongue cancer tissue samples were K36-positive. Immunostaining also revealed that K36 was expressed in nail beds, Hassal's corpuscles in the thymus and the hair cortex. However, K36 was not expressed in the squamous epithelia of the skin, cervix and oesophagus, and the squamous cells of cervical carcinomas, basal cell carcinoma or melanoma. The present data indicated that K36 may be inactivated in tumours of the tongue. However, whether this is part of the tumoural process or if it is an effect of the tumour itself remains to be elucidated.

Squamous cell carcinoma in the anophthalmic socket: a series of four cases with HPV-16 profiling

PurposeTo present the clinical and histological features of squamous cell carcinoma (SCC) in the anophthalmic socket in four adult patients, and to determine the presence of human papillomavirus infection (HPV).MethodsRetrospective...

SQUAMOUS CELL CARCINOMA IN THE FOOT: CASE SERIES AND LITERATURE REVIEW.

ABSTRACTObjectives:To report a case series of squamous cell carcinoma (SCC) in the foot, describing previous risk factors, surgical treatment, histopathological findings, and functional and oncological results. Methods:Nine consecutive patients diagnosed with SCC of the foot were treated at a single institution and prospectively analyzed for risk factors related to the disease, surgical outcome, and histopathological, functional and oncological results. All patients had identifiable risk factors for SCC. Results:Definitive treatment consisted of partial (6 patients) or total (3 patients) amputation of the foot. The functional score was good or excellent in the surviving patients. Early identifiable risk factors are present in most patients. Biopsy when this diagnosis is suspected, in association with oncological principles, avoids diagnostic and treatment errors. Conclusion:Despite delayed diagnosis and surgical treatment with partial and total amputations of the foot in our series, we observed good oncological outcomes that avoided systemic spread of the disease and achieved expected functional results. Level of Evidence V; Case series.

Matrix metalloproteinase 1: a better biomarker for squamous cell carcinoma by multiple microarray analyses.

The present study aimed to validate MMP1 role in the development of squamous cell carcinoma (SCC) by bioinformatics methods. Gene expression data of 10 GSE series (5 HNSCCs and 5 cSCCs) were obtained from the Gene Expression Omnibus (GEO) database and used to identify differentially expressed genes (DEGs). Higher expression of MMP1 was found rank number one in 9/10 GSE series of SCC. MMP1 was mainly focused on Gene Ontology (GO) terms of collagen catabolic process, extracellular matrix disassembly. The analysis results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways mainly involved Rheumatoid arthritis, Bladder cancer and Pathways in cancer. Also, MMP1 was identified as a hub protein in the PPI network by using Cytoscape software. In addition, others MMPs members of family were analyzed. These results suggested that MMP1 may be pivotal to the transition from normal skin to premalignant lesions to SCC, thus representing a potential therapeutic target gene of diagnosis and prevention in SCC.

Transoral laser microsurgery for oropharyngeal squamous cell carcinoma: A paradigm shift in therapeutic approach.

The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM). A consecutive series of patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013 was studied. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival analyses were evaluated using Kaplan-Meier statistics. Tumor subsites included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC) stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was 1.3%. To the best of our knowledge, this is the largest single-center TLM oropharyngeal SCC series to date. Our data suggest that TLM +/- postoperative radiotherapy (PORT) results in at least as good oncologic outcomes as chemoradiotherapy (CRT), while conferring swallowing function advantages. © 2016 Wiley Periodicals, Inc. Head Neck , 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38:1263-1270, 2016.

Follicular cutaneous squamous cell carcinoma: an under-recognized neoplasm arising from hair appendage structures

Cutaneous squamous cell carcinoma (SCC) with no demonstrable point of epidermal origin is problematic as it raises consideration of metastatic SCC histologically. There are rare case reports and series of SCC arising from the wall of hair follicle structures. Such lesions have been termed follicular SCC (FSCC). To investigate the clinicopathological features of FSCC. We prospectively collected cases of follicular SCC over a 5-year period. Follicular SCC is defined as a cutaneous SCC deriving from a pre-existing hair follicle structure. Lesions were considered to represent 'hybrid' SCCs if an interfollicular epidermal origin was also demonstrated; SCCs with >50% of the origin from interfollicular epidermis were excluded. Histological features and clinical information were evaluated. We identified 61 cases of follicular SCC arising in 60 patients from a database of 5212 cutaneous SCCs encountered over the same time period by the same authors. There were 49 pure follicular SCCs and 12 hybrid lesions. The male to female ratio was 44:16; the mean age was 74years (range 44-93). Follicular SCC represents 1·2% of all primary SCCs. Biopsies of such lesions, if the appendage structure of origin is not represented, are histologically indistinguishable from metastatic SCC. Recognition of this under-reported form of SCC is essential if an inappropriate diagnosis of metastatic SCC, with potentially harmful and inappropriate therapy and investigation, is to be avoided.

Margin mapping in transoral surgery for head and neck cancer

To evaluate the results of patients treated by transoral laser microsurgery and margin mapping with attention to deep margin dimensions in the lateral pharyngeal wall. A microscopic margin analysis of multiblock surgical specimens applied to a prospectively accrued case series of squamous cell carcinoma of the palatine tonsils. There were 128 tonsil cancers analyzed that were removed transorally, using microscopic margin mapping by surgeon and pathologist. The closest deep and peripheral margins were assessed. The results were then related to a study of the normal dimensions of the lateral pharyngeal wall in 20 healthy patients using magnetic resonance imaging. Outcome measures included number of positive margins, narrowest margin, local control, and disease-free and overall survival. The average closest margin was 1.98 mm (range, 0.30-6.50 mm) deep and 2.82 mm (range, 1.00-5.00 mm) peripheral. There was one positive margin encountered in the previously untreated group (1%), and one local recurrence ultimately developed. Radiographic measures revealed a mean minimal thickness of the lateral pharyngeal wall musculature of 2.4 mm. With mean follow-up of 4.3 years (range, 2-14 years), the 5-year estimate for local control is 99%, disease-free survival is 94.5%, and overall survival is 76%. Margin mapping achieves a low rate of positive margins and is associated with good local control. Based on lateral pharyngeal wall anatomy, wide margins are often unobtainable and may be unnecessary so long as the final inked margin is clear. 4.

Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas.

The transcription factor interferon regulatory factor 6 (IRF6) regulates craniofacial development and epidermal proliferation. We recently showed that IRF6 is a component of a regulatory feedback loop that controls the proliferative potential of epidermal cells. IRF6 is transcriptionally activated by p63 and induces its proteasome-mediated down-regulation, thereby limiting keratinocyte proliferative potential. We hypothesized that IRF6 may also be involved in skin carcinogenesis. Hence, we analyzed IRF6 expression in a large series of squamous cell carcinomas (SCCs) and found a strong down-regulation of IRF6 that correlated with tumor invasive and differentiation status. IRF6 down-regulation in SCC cell lines and primary tumors correlates with methylation on a CpG dinucleotide island located in its promoter region. To identify the molecular mechanisms regulating IRF6 potential tumor suppressive activity, we performed a genome-wide analysis by combining ChIP sequencing for IRF6 binding sites and gene expression profiling in primary human keratinocytes after siRNA-mediated IRF6 depletion. We observed dysregulation of cell cycle-related genes and genes involved in differentiation, cell adhesion, and cell-cell contact. Many of these genes were direct IRF6 targets. We also performed in vitro invasion assays showing that IRF6 down-regulation promotes invasive behavior and that reintroduction of IRF6 into SCC cells strongly inhibits cell growth. These results indicate a function for IRF6 in suppression of tumorigenesis in stratified epithelia.

SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer

The transcription factor SOX2 (3q26.3–q27) is a key regulator of foregut development and an embryonic stem cell factor cooperating during induction of pluripotency in terminally differentiated somatic cells. Recently, we found SOX2 to be amplified in a subset of squamous cell lung and esophageal cancers. The aim of this study was to explore the prognostic role of SOX2 in a large series of squamous cell carcinomas and adenocarcinomas of the lung. A total of 891 samples from two independent population-based cohorts were assessed by fluorescence in situ hybridization and immunohistochemistry. Furthermore, we assessed for associations between SOX2 amplification/upregulation and clinicopathological features. Similar results were found in the two cohorts. Within squamous cell carcinoma cases, 8% high-level as well as 68 and 65% low-level SOX2 amplifications occurred in the two cohorts, respectively. In adenocarcinomas, no high-level amplification was found and low-level amplification occurred in 6% of the two cohorts. Within squamous cell carcinomas of one cohort, SOX2 amplification was associated with lower tumor grade, while higher levels of SOX2 expression were related to younger age, smaller tumor size, and lower probability of angiolymphatic invasion and metastasis. High SOX2 expression levels proved to be a marker for prolonged overall survival among patients with squamous cell carcinomas. In conclusion, SOX2 amplification and upregulation are frequent events in squamous cell carcinomas of the lung and are associated with indicators of favorable prognosis.

Abstract 2251: High VEGFA pathway expression predicts good prognosis in stage I squamous cell carcinoma of the lung

Abstract Vascular endothelial growth factor A (VEGFA) mediates its effects through VEGFR1 and VEGFR2, regulating angiogenesis in healthy and tumor tissues. Hence, an anti-VEGFA therapy has been approved, in combination with platinum-based chemotherapy, as first line treatment in unresectable advanced non-small cell lung cancer (NSCLC). This antiangiogenic therapy is based on the inactivation of the VEGFA pathway in endothelial cells. However, tumor cells also express VEGFA and its receptors. In fact, the relationship between NSCLC prognosis and the expression of VEGFA and its receptors has been widely studied. However, the results are controversial. The lack of agreement may be due to variations in gene expression, response to therapy or outcome between the different NSCLC histological subtypes. Moreover, different oxygen requirements in early versus late stages of the disease may profoundly influence the relevance of the VEGFA pathway in NSCLC. The aim of this study was to analyze the prognostic significance of the activation of the VEGFA pathway in early NSCLC by means of the development of a VEGFA signaling score that reflects the activation of VEGFA pathway in tumor cells. A second objective was to clarify the prognostic relevance of this pathway in the two main histological subtypes, adenocarcinoma (ADC) and squamous cell carcinoma (SCC), separately. To this purpose, we analyzed the VEGFA signaling score in three series of NSCLC patients: 1) a series of 298 stage I-IIIA NSCLC patients recruited in the context of the European Early Lung Cancer (EUELC) project; 2) a first validation series of 173 stage I-IIIA NSCLC patients from the MD Anderson Cancer Center; and 3) a second validation series of 50 patients stage I SCC from the CHU Hospital. Immunohistochemistry was used to detect VEGFA, VEGFR1, VEGFR2, and results were analyzed by semiquantitative methods. The VEGFA signaling score was calculated as the sum of VEGFA, VEGFR1 and VEGFR2 scores. In the EUELC series, the multivariate analysis, using the Fine & Gray adaptation of Cox proportional hazard model, revealed that high VEGFA signaling score is an independent good prognostic factor for progression-free survival (HR=0.61 [0.41-0.91], p=0.01). Sub-group analysis revealed that the favorable prognostic value of VEGFA signaling score was restricted to SCC patients (HR=0.40 [0.20-0.78], p=0.007). Conversely, this association was not observed in ADC cases (HR=0.83 [0.48-1.45], p=0.52). The strong association between high VEGFA signaling score and longer recurrence-free survival among stage I SCC patients was validated in the MD Anderson series (HR=0.05 [0.004-0.62], p=0.02). In the stage I SCC series of the CHU Hospital the same tendency was found (p=0.08). In conclusion, these data point to different roles of VEGFA and its receptors in the biology of the two main histological types of lung cancer, and suggests a paradigm shift in the role of the VEGFA pathway in SCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2251. doi:10.1158/1538-7445.AM2011-2251

Significance of Jab1 Expression in Human Esophageal Squamous Cell Carcinoma

The aim of the present study was to examine the expression of Jun activation domain-binding protein 1(Jab1) and p27 and to elucidate its clinicopathologic significance in a larger series of squamous cell carcinoma (SCC) of the esophagus. Reduced expression of p27 has been associated with poor prognosis in most human cancers, including esophageal SCCs. Jab1 is known as a coactivator of AP-1 transcription factor, which contributes to tumor progression by degrading the p27 protein. Immunohistochemical and Western blot analysis were performed in 90 cases of esophageal SCCs and ECA109 cells. Survival analyses were performed by using the Kaplan-Meier method. Immunohistochemical analysis showed that Jab1 expression was negatively associated with p27 level and significantly associated with unfavorable clinicopathologic variables. Overexpression of Jab1 in ECA109 cells resulted in decreased p27 level and this decrease was sensitive to 26S proteasome inhibitors. Subcellular fractionation confirmed Jab1 could lead to nuclear export of p27. Survival analysis revealed that Jab1 overexpression was significantly associated with overall survival (P<0.001). When Jab1 and p27 are combined, patients with Jab1(+)/p27(-) revealed poorer overall survival (P<0.001), what's more, patients with the phenotype of Jab1(+)/lymph node(+) had poorer disease-free and overall survival than others (P<0.001). These findings suggest that Jab1 is involved in the pathogenesis of esophageal SCC and that elevated levels of Jab1 expression may indicate a poor prognosis for patients with esophageal SCC.

Comparative analysis of c‐erbB‐2 (HER‐2/neu) in squamous cell carcinoma of the tongue: does over‐expression exist? And what is its correlation with traditional diagnostic parameters?

Over-expression of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in many kinds of cancer, whereas conflicting data exist about the prevalence of HER-2/neu over-expression in squamous cell carcinoma (SCC) of the tongue. The status of Her-2/neu was evaluated in a series of SCC of the tongue to verify the frequency of over-expression of HER-2/neu and evaluate the correlation with traditional diagnostic parameters of this neoplasm. Fourty patients with SCC of the tongue were investigated for over-expression of the protein through immunohistochemistry using CB11 antibody, the Hercep Test kit and FISH. Data obtained using the Hercep Test differ from published reports concerning the over-expression of Her-2/neu and there was no correlation between levels of expression of Her-2/neu and other clinico-pathological and/or prognostic parameters. Of the 40 specimens, using CB11 we obtained results in line with published reports; however, with the Hercep Test we found only 1 positive case (2.5%) (score 3+). These data, confirmed by FISH, suggest that Her-2/neu is not a suitable marker that could play a primary role in the clinical-therapeutic management of SCC of the tongue.

Chromatin assembly factor‐1 (CAF‐1)‐mediated regulation of cell proliferation and DNA repair: a link with the biological behaviour of squamous cell carcinoma of the tongue?

Squamous cell carcinoma (SCC) of the tongue shows aggressive behaviour and a poor prognosis. Clinicopathological parameters fail to provide reliable prognostic information, so the search continues for new molecular markers for this tumour. Chromatin assembly factor-1 (CAF-1) plays a major role in chromatin assembly during cell replication and DNA repair and has been proposed as a new proliferation marker. The aim of this study was to investigate its expression in SCC of the tongue. The immunohistochemical expression of the p60 and p150 subunits of CAF-1 were evaluated in a series of SCCs of the tongue. The findings were correlated with the expression of proliferation cell nuclear antigen (PCNA) and patients' clinicopathological and follow-up data. CAF-1/p60 was expressed in all the tumours, whereas CAF-1/p150 was down-regulated in a number of cases. Overexpression of CAF-1/p60 and down-regulation of CAF-1/p150 identified SCCs with poor outcome, in addition to the classical prognostic parameters. Simultaneous CAF-1-mediated deregulation of cell proliferation and DNA repair takes place in aggressive SCC of the tongue. Therefore, the evaluation of CAF-1 expression may be a valuable tool for evaluation of the biological behaviour of these tumours. This may be relevant to the introduction of improved follow-up protocols and/or alternative therapeutic regimens.

Sentinel Lymph Node Biopsy in Cutaneous Squamous Cell Carcinoma

BACKGROUND Although most cutaneous squamous cell carcinoma (SCC) is curable by a variety of treatment modalities, a small subset of tumors recur, metastasize, and result in death. Although risk factors for metastasis have been described, there are little data available on appropriate workup and staging of patients with high-risk SCC. OBJECTIVE We reviewed reported cases and case series of SCC in which sentinel lymph node biopsy (SLNB) was performed to determine whether further research is warranted in developing SLNB as a staging tool for patients with high-risk SCC. METHODS The English medical literature was reviewed for reports of SLNB in patients with cutaneous SCC. Data from anogenital and nonanogenital cases were collected and analyzed separately. The percentage of cases with a positive sentinel lymph node (SLN) was calculated. False negative and nondetection rates were tabulated. Rates of local recurrence, nodal and distant metastasis, and disease-specific death were reported. RESULTS A total of 607 patients with anogenital SCC and 85 patients with nonanogenital SCC were included in the analysis. A SLN could not be identified in 3% of anogenital and 4% of nonanogenital cases. SLNB was positive in 24% of anogenital and 21% of nonanogenital patients. False-negative rates as determined by completion lymphadenectomy were 4% (8/213) and 5% (1/20), respectively. Most false-negative results were reported in studies from 2000 or earlier in which the combination of radioisotope and blue dye was not used in the SLN localization process. Complications were reported rarely and were limited to hematoma, seroma, cutaneous lymphatic fistula, wound infection, and dehiscence. CONCLUSIONS Owing to the lack of controlled studies, it is premature to draw conclusions regarding the utility of SLNB in SCC. The available data, however, suggest that SLNB accurately diagnoses subclinical lymph node metastasis with few false-negative results and low morbidity. Controlled studies are needed to demonstrate whether early detection of subclinical nodal metastasis will lead to improved disease-free or overall survival for patients with high-risk SCC.

Sentinel Lymph Node Biopsy in Cutaneous Squamous Cell Carcinoma: A Systematic Review of the English Literature

Although most cutaneous squamous cell carcinoma (SCC) is curable by a variety of treatment modalities, a small subset of tumors recur, metastasize, and result in death. Although risk factors for metastasis have been described, there are little data available on appropriate workup and staging of patients with high-risk SCC. We reviewed reported cases and case series of SCC in which sentinel lymph node biopsy (SLNB) was performed to determine whether further research is warranted in developing SLNB as a staging tool for patients with high-risk SCC. The English medical literature was reviewed for reports of SLNB in patients with cutaneous SCC. Data from anogenital and nonanogenital cases were collected and analyzed separately. The percentage of cases with a positive sentinel lymph node (SLN) was calculated. False negative and nondetection rates were tabulated. Rates of local recurrence, nodal and distant metastasis, and disease-specific death were reported. A total of 607 patients with anogenital SCC and 85 patients with nonanogenital SCC were included in the analysis. A SLN could not be identified in 3% of anogenital and 4% of nonanogenital cases. SLNB was positive in 24% of anogenital and 21% of nonanogenital patients. False-negative rates as determined by completion lymphadenectomy were 4% (8/213) and 5% (1/20), respectively. Most false-negative results were reported in studies from 2000 or earlier in which the combination of radioisotope and blue dye was not used in the SLN localization process. Complications were reported rarely and were limited to hematoma, seroma, cutaneous lymphatic fistula, wound infection, and dehiscence. Owing to the lack of controlled studies, it is premature to draw conclusions regarding the utility of SLNB in SCC. The available data, however, suggest that SLNB accurately diagnoses subclinical lymph node metastasis with few false-negative results and low morbidity. Controlled studies are needed to demonstrate whether early detection of subclinical nodal metastasis will lead to improved disease-free or overall survival for patients with high-risk SCC.

Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours

The molecular mechanisms that underlie the development of squamous cell skin cancers (SSC) are poorly understood. We have used oligonucleotide microarrays to compare the differences in cellular gene expression between a series of keratinocyte cell that mimic disease progression with the aim of identifying genes that may potentially contribute towards squamous cell carcinoma (SCC) progression in vivo, and in particular to identify markers that may serve as potential therapeutic targets for SCC treatment. Gene expression differences were corroborated by polymerase chain reaction and Western blotting. We identified Axl, a receptor tyrosine kinase with transforming potential that has also been shown to have a role in cell survival, adhesion and chemotaxis, was upregulated in vitro in SCC-derived cells compared to premalignant cells. Extending the investigation to tumour biopsies showed that the Axl protein was overexpressed in vivo in a series of SCCs.

Cutaneous squamous cell carcinoma treated with Mohs micrographic surgery in Australia I. Experience over 10 years

Only a few reports have been published on the long-term outcome of surgical excision of cutaneous squamous cell carcinoma (SCC). Our purpose was to report the clinical findings and 5-year recurrence rate of all patients with cutaneous SCC treated with Mohs micrographic surgery (MMS) in Australia between 1993 and 2002. This prospective, multicenter case series included all patients with SCC who were monitored by the Skin and Cancer Foundation. The main outcome measures were patient demographics, reason for referral, duration of tumor, site, preoperative tumor size, postoperative defect size, recurrences before MMS, histological subtypes, and 5-year recurrence after MMS. The case series comprised 1263 patients (25.7% female and 74.3% male; P < .0001) with a mean age of 66 +/- 13 years. In 61.1% of cases the lesion was a primary tumor, and in 38.9% it was a recurrent tumor. Most of the tumors (96.5%) were on the head and neck area. Recurrent tumors were larger than primary tumors (P < .0001), had a larger postexcision defect (P < .0001), required more levels of excision (P < .0001), and had more cases of subclinical extension (P = .002). Recurrence after MMS was diagnosed in 15 of the 381 patients (3.9%) who completed the 5-year follow-up after MMS. The recurrence rate was 2.6% in patients with primary SCC and 5.9% in patients with previously recurrent SCC (P < .001). This large prospective series of SCC managed by MMS is characterized by a high percentage of high-risk tumors. The low 5-year recurrence rate with MMS emphasizes the importance of margin-controlled excision.

Loss of Fhit Expression in Squamous Cell Carcinoma and Premalignant Lesions of the Larynx

The tumor suppressor gene FHIT (fragile histidine triad) at chromosomal position 3p14.2 is altered by deletions in human tumors. The frequency and specificity of its inactivation vary among carcinomas, but few articles have referred to premalignant lesions such as dysplasia. We studied the expression of FHIT in a series of squamous cell carcinomas and premalignant lesions of the larynx. We observed 36 laryngeal carcinoma biopsy specimens and 70 dysplasia biopsy specimens. We studied FHIT expression in carcinoma and dysplasia with the immunohistochemical ABC (avidin-biotinylated peroxidase complex) method. Loss of FHIT protein was observed in 42% of the squamous cell carcinomas and 23% of the premalignant lesions. There was no significant difference among the three grades of dysplasia in FHIT expression. These findings of loss of FHIT protein expression, not only in squamous cell carcinoma, but also in premalignant lesions, indicate that FHIT alterations play an important role in the early events of carcinogenesis.