Characterization Of Squamous Cell Carcinoma Research Articles

Molecular characterization of squamous cell carcinoma of the anal canal.

Squamous cell carcinoma of the anal canal (SCCA) is an uncommon malignancy with limited therapeutic options. Nivolumab and pembrolizumab show promising results in patients with SCCA. Human papillomavirus (HPV)-negative tumors are frequently TP53-mutated (TP53-MT) and often resistant to therapy. We present a large molecularly-profiled cohort of SCCA, exploring the underlying biology of SCCA, differences between TP53-wild type (TP53-WT) and TP53-MT tumors, and differences between local and metastatic tumors. SCCA specimens (n=311) underwent multiplatform testing with immunohistochemistry (IHC), in situ hybridization (ISH) and next-generation sequencing (NGS). Tumor mutational burden (TMB) was calculated using only somatic nonsynonymous missense mutations. Chi-square testing was used for comparative analyses. The most frequently mutated genes included PIK3CA (28.1%), KMT2D (19.5%), FBXW7 (12%), TP53 (12%) and PTEN (10.8%). The expression of PD-1 was seen in 68.8% and PD-L1 in 40.5% of tumors. High TMB was present in 6.7% of specimens. HER2 IHC was positive in 0.9%, amplification by chromogenic in situ hybridization (CISH) was seen 1.3%, and mutations in ERBB2 were present in 1.8% of tumors. The latter mutation has not been previously described in SCCA. When compared with TP53-WT tumors, TP53-MT tumors had higher rates of CDKN2A, EWSR1, JAK1, FGFR1 and BRAF mutations. PD-1 and PD-L1 expression were similar, and high TMB did not correlate with PD-1 (P=0.50) or PD-L1 (P=0.52) expression. Molecular profiling differences between TP53-MT and TP53-WT SCCA indicate different carcinogenic pathways which may influence response to therapy. Low frequency mutations in several druggable genes may provide therapeutic opportunities for patients with SCCA.

Cytological and histopathological characterization of squamous cell carcinoma from mammary region in a male dog : A case study

Cancer is a fatal malignant disturbance of growth and one of the major causes of morbidity and mortality among canines. Squamous cell carcinoma (SCC) is relatively more common and a highly malignant neoplasm, known to affect dogs. However, SCC of the mammary region is rare in occurrence in both veterinary and human medicine. The present study describes a case of well differentiated SCC of the mammary region in a male dog. An eleven-year-old intact male Pit Bull was presented in Veterinary Polyclinic Lalhri Distt Una, with a history of multiple cutaneous ulcerative lesions in the region of right posterior mammary gland. Fine needle aspiration and touch impression cytology smears were stained with giemsa examined on the day of presentation revealed large number of malignant squamous epithelial cells occurring either individually or in clusters exhibiting marked pleomorphism, anisocytosis and anisokaryosis suggestive of SCC. Surgical resection of the lesion involving mammary tissue was done. The excised mass grossly presented as grayish, irregular in size, lobulated subcutaneous tissue. The representative tissue pieces preserved in 10% neutral buffered formalin were subjected to histopathological evaluation. Histopathological examination revealed cords and nests of proliferating neoplastic cells in the dermis consisting of immature polyhedral cells at the periphery and eosinophilic laminated keratin pearls at the centre separated by thin fibrous tissue stroma confirmed it for well differentiated form of SCC. The diagnosis of a well differentiated SCC was made on the basis of cytological findings and further confirmed on histopathological evaluation besides special staining.

Molecular genetics of head and neck squamous cell carcinoma.

The aim of this review is to summarize the current knowledge on the genomic characterization of squamous cell carcinomas of the head and neck (HNSCC) and discusses how these abnormalities could be incorporated into a therapeutic approach. Tobacco and HPV infection, the two main risk factors of HNSCC, allow the definition of two groups with distinct anatomoclinical and genetic features. As tobacco and HPV infection are not exclusive, exposure to both risk factors is associated with an intermediate prognostic. HPV-positive, nontobacco-related HNSCCs are associated with a better prognosis, a rather more simple genomic profile, frequent activating mutations of genes involved in pi3kinase pathway, and the very low incidence of mutations of tumor suppressor genes. HPV-negative, tobacco-related HNSCC are genetically more complex. HPV-negative HNSCC are characterized by almost mandatory inactivating mutations/deletions of tumor suppressor genes (especially TP53 and CDKN2A) and the occurrence, though less frequent, of activating mutations or amplifications of some oncogenes that encode for cell cycle proteins or receptors with tyrosine kinase activity. Despite many efforts to improve therapeutic targeting in RM HNSCC, Cetuximab, a monoclonal antibody targeting REGF, remains the sole approved targeted treatment in RM HNSCC. Despite the increasingly precise genomic characterization of HNSCCs, precision medicine is struggling to find its place in the management of HNSCCs. Inclusion of enriched populations in dedicated trials is likely to help implement precision medicine in the management of HNSCCs.

Immunohistochemical staining patterns of alpha-keratins in normal tissues from two reptile species: implications for characterization of squamous cell carcinomas

BackgroundCytokeratins with epitopes in common with those of alpha (acidic and basic) mammalian keratins have been immunohistochemically demonstrated in the epidermis of reptiles. However, there are no reports of immunohistochemical staining patterns of alpha-keratins in other tissues from reptiles. Because the epithelial tumours usually retain the keratin patterns of their normal epithelial origin, it is necessary to know in advance these patterns in the major normal epithelia and organs. We used anti-alpha human keratin AE1 and AE3 monoclonal antibodies to study the staining patterns of alpha-keratins in the major normal epithelia and organs from two reptile species [the bearded dragon (Pogona vitticeps) and the loggerhead sea turtle (Caretta caretta)]. We also studied the immunolocalization of alpha-keratins in squamous cell carcinomas (SCCs) in a bearded dragon and two loggerhead turtles.ResultsAcidic alpha-keratin (AE1 positive) was detected in many of the epithelial tissues of the bearded dragons; however, the detection of basic alpha-keratin (AE3 positive) was much more limited. Alpha-keratins were detected in a greater number of tissues of loggerhead turtles compared with those observed in bearded dragons. In the bearded dragon SCC, all layers of the nests of neoplastic cells, including the cornified layer of the keratin pearls, were strongly reactive with the AE1 antibody. However, a weak reactivity using the AE3 antibody was detected in the basal and intermediate layers of these nests. In the cutaneous SCCs of both sea turtles, acidic alpha-keratin was detected in the basal and suprabasal layers, and in all of the invasive neoplastic cords, while basic alpha-keratin was mainly detected in the invasive neoplastic cords. The pattern observed in the metastases in both turtles consisted of immunohistological detection of acidic alpha-keratin in all metastatic foci, and limited or lack of detection of basic alpha-keratin.ConclusionsThis study provides, for the first time, information about the immunohistochemical staining patterns of alpha-keratins in normal tissues from bearded dragons and loggerhead sea turtles, and confirms the usefulness of AE1 and AE3 monoclonal antibodies in these reptile species. The use of these antibodies also contributed to a better characterization of SCCs in these species.

Molecular characterization of squamous cell carcinoma of the anal canal (SCCA).

538 Background: Nivolumab has shown promising results in SCCA patients. The majority of SCCA cases have been linked to prior human papillomavirus (HPV) infection. However, HPV negative tumors are frequently TP53 mutated and often resistant to therapy. Molecular characteristics of SCCA are largely undefined. Here we explored the underlying biology of SCCA and the differences between TP53-wild type ( TP53-WT) and TP53-mutated ( TP53-MT) tumors. Methods: SCCA specimens underwent multiplatform testing with protein expression (IHC), gene amplification (ISH), and sequencing (NGS). Tumor mutational burden (TMB) was calculated using only somatic nonsynonymous missense mutations. Chi-square tests were used for comparative analyses. Results: In total, 253 tumors were studied. The most frequently mutated genes included PIK3CA (24%), BRCA2 (14%), FBXW7 (12.4%), TP53 (9.7%), and PTEN (8.9%). In a subset of 23 tumors subjected to Illumina NextSeq (592 gene) testing, the most common mutations were NOTCH2 (30%), NOTCH1 (27.3%), POLE (21.7%) , TSC2 (17.4%), PTEN (14.3%), BRAF (13.6%), BRCA2 (13.0%), PIK3CA (13.0%), and FBXW7 (9.5%). Tumors frequently expressed MRP1 (97.6%), EGFR (92.7%), TOP2A (88.5%), TOPO1 (69.5%), MGMT (67.8%), and RRM1 (59.9%). Expression of PD-1 was seen in 55.8% (24/43) of tumors, and PD-L1 in 15.4% (9/34). HER2 was amplified in 2% (3/147) of samples, which has not been previously described in SCCA. When compared with TP53-WT (n = 93) tumors, T P53-MT (n = 10) had higher rates of BRAF (22% vs. 1%, p < 0.001) and RB1 mutations (44% vs. 0%, p < 0.001), whereas TP53-WT had higher expression of TOPO1 (76% vs. 40%, p = 0.01) and TUBB3 (19% vs. 50%, p = 0.02). There were no differences between the two groups in the frequency of PD-1 or PD-L1 expression. Mean TMB was 8.6 mutations/megabase and, using a TMB cut-off > 17 mutations/megabase to define high vs. low TMB, 6.7% of tumors were TMB-High. High TMB did not correlate with PD-1 (p = 0.50) or PD-L1 status (p = 0.52). Conclusions: Molecular profiling differences between TP53-MT and TP53-WT SCCA indicate different carcinogenic pathways and biology, which may influence response to therapy. Low frequency mutations in several druggable genes may provide therapeutic opportunities for patients with SCCA.

Abstract 3692: Transcriptome analysis of oral tongue cancer reveals novel insights into wild type and mutant TP53 transcription program

Abstract The p53 oncoprotein is a tumor suppressor that is stabilized upon various forms of cellular stresses to induce transcription of genes regulating cell cycle arrest or apoptosis. TP53 is the most frequently mutated gene in human cancers and majority of mutations are located in the region encoding the DNA binding domain compromising thereby its transcription activation ability and resulting in loss of function. Recent studies however suggest mutant p53 proteins to exhibit a gain of function property. Specific p53 missense mutations can result in an altered transcription program causing positive regulation of cell proliferation, metastasis and chemoresistance. In our previous studies, we performed comprehensive characterization of squamous cell carcinoma of the oral tongue (SCCOT) with respect to p53, EGFR, Wnt, MSI, LoH of several tumor suppressor loci and HPV status. Mutant p53 was a significant predictor of overall survival and the TP53 codon 72 Proline allele was significantly associated with SCCOT. In order to dissect the role of mutant p53 in tongue cancer, we performed genome wide DNA and RNA profiling of 26 and 40 SCCOT samples, respectively. Both mutant and wild type tumor samples appeared to exhibit comparable levels of DNA copy number alterations. Transcriptome data analyses using a combination of single sample gene set enrichment analysis and comparative marker selection revealed gene sets that could significantly distinguish p53 mutant and wild type tumor samples. Significance analysis of microarrays performed on all genes constituting the differentially enriched gene sets surprisingly identified only two genes to be upregulated in p53 mutant samples at a false discovery rate significantly lower than 10% namely TP53 itself and SMARCD1; the latter a member of the SWI/SNF chromatin remodelling complex. Elevated levels of TP53 transcript in tumors harbouring mutant p53 significantly correlated with levels of ZMAT3, itself induced by p53 and known to stabilize the TP53 transcript. In addition, the analysis revealed several known (ATF3 and others) and novel (GCHFR and others) targets of wild type p53. Differential expression of all targets was validated in additional tongue cancer samples. Ectopic expression of certain (but not all) p53 mutant proteins in p53 null cells induced SMARCD1 (but not canonical wild type p53 targets) while expression of wild type p53 induced GCHFR, ATF3, CDKN1A, etc. (but not SMARCD1). In contrast, p53 stabilization in cells harboring wild type p53 caused elevation of GCHFR, ATF3, CDKN1A, etc., but not of SMARCD1. Validation of novel targets using promoter-luciferase constructs, chromatin immunoprecipitation PCR and a tongue cancer tissue microarray is underway. This is perhaps the first evidence from Head and Neck tumor samples for a gain of function activity of mutant p53. Thus wild type and mutant p53 may support distinct transcription programs in tongue cancer. Citation Format: Raju SR Adduri, Padmavathi Kavadipula, Viswakalyan Kotapalli, Leena Bashyam, Anupama Shirke, Arun kumar Paripati, Swarnalata Gowrishankar, Mukta Srinivasulu, Mohammed Mujtaba Ali, Subramanyeshwar Rao, Snehalatha Dhagam, Mohana Vamsy Chigurupati, Shantveer G. Uppin, Vijaya Tourani, Murali D. Bashyam. Transcriptome analysis of oral tongue cancer reveals novel insights into wild type and mutant TP53 transcription program. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3692.

Extensive integrated molecular characterization of squamous cell carcinoma and adenocarcinoma of the cervix from within The Cancer Genome Atlas (TCGA): The Cancer Genome Atlas (TCGA) Cervical Analysis Working Group

Extensive integrated molecular characterization of squamous cell carcinoma and adenocarcinoma of the cervix from within The Cancer Genome Atlas (TCGA): The Cancer Genome Atlas (TCGA) Cervical Analysis Working Group

Using Texture Analysis to Determine Human Papillomavirus Status of Oropharyngeal Squamous Cell Carcinomas on CT.

Human papillomavirus-associated oropharyngeal squamous cell carcinoma is increasing in prevalence and typically occurs in younger patients than human papillomavirus-negative squamous cell carcinoma. While imaging features of human papillomavirus-positive versus human papillomavirus-negative squamous cell carcinoma nodal metastases have been described, characteristics distinguishing human papillomavirus-positive from human papillomavirus-negative primary squamous cell carcinomas have not been well established. The purpose of this project was to evaluate the use of texture features to distinguish human papillomavirus-positive and human papillomavirus-negative primary oropharyngeal squamous cell carcinoma. Following institutional review board approval, 40 patients with primary oropharyngeal squamous cell carcinoma and known human papillomavirus status who underwent contrast-enhanced CT between December 2009 and October 2013 were included in this study. Segmentation of the primary lesion was manually performed with a semiautomated graphical-user interface. Following segmentation, an in-house-developed texture analysis program extracted 42 texture features from each segmented volume. A t test was used to evaluate differences in texture parameters between human papillomavirus-positive and human papillomavirus-negative squamous cell carcinomas. Of the 40 included patients, 29 had human papillomavirus-positive oropharyngeal squamous cell carcinoma and 11 had human papillomavirus-negative oropharyngeal squamous cell carcinoma. Significant differences were seen in the histogram parameters median (P = .006) and entropy (P = .016) and squamous cell carcinoma entropy (P = .043). There are statistically significant differences in some texture features between human papillomavirus-positive and human papillomavirus-negative oropharyngeal tumors. Texture analysis may be considered an adjunct to the evaluation of human papillomavirus status and characterization of squamous cell carcinoma.

Characterization of squamous cell carcinomas of the head and neck using methods of spatial statistics.

In the present study, 53 cases of squamous cell carcinomas of the head and neck were characterized by a quantitative histological texture analysis based on principles of spatial statistics. A planar tessellation of the epithelial tumour component was generated by a skeletonization algorithm. The size distribution of the virtual cells of this planar tessellation, and the size distribution of the profiles of the tumour cell nuclei were estimated in terms of area and boundary length. The intensity, the reduced second moment function (K-function) and the pair correlation function of the point process of the centroids of the profiles of the tumour cell nuclei were also estimated. For both purposes, it is necessary to correct for edge effects, which we consider in this paper in some detail. Specifically, the point patterns of the tumour cell nuclei were considered as realizations of a point process, where the points exist only in the epithelial tumour component (the permitted phase) and not in the stroma (the forbidden phase). The methods allow to characterize each individual tumour by a series of summary statistics. The total set of cases was then partitioned into two groups: 19 cases without lymph node metastases (pN0), and 34 nodal positive cases (pN1 or pN2). Statistical analysis showed no significant differences between the intensities, the mean K-functions and the mean pair correlation functions of the tumour cell nucleus profiles of the two groups. However, there were some significant differences between the sizes of the virtual cells and of the nucleus profiles of the nodal negative cases as compared to the nodal positive cases. In a logistic regression analysis, one of the quantitative nuclear size variables (mean nuclear area) was found to be a significant predictor of lymph node metastasis, in addition to tumour stage. The study shows the potential of methods of spatial statistics for objective quantitative grading of squamous cell carcinomas of the head and neck, and provides an example for modelling histological point patterns as realizations of planar point processes occupying a reference phase which is only a partial component of the total tissue.

Characterization of squamous cell carcinoma in an organotypic culture via subsurface non-linear optical molecular imaging

Tristetraprolin (TTP) is an RNA-binding protein which downregulates multiple cytokines that mediate progression of head and neck squamous cell carcinoma (HNSCC). We previously showed that HNSCC cells with shRNA-mediated knockdown of TTP are more invasive than controls. In this study, we use control and TTP-deficient cells to present a novel subsurface non-linear optical molecular imaging method using a three-dimensional (3D) organotypic construct, and compare the live cell imaging data to histology of fixed tissue specimens. This manuscript describes how to prepare and image the novel organotypic system that closely mimics HNSCC in a clinical setting. The oral cancer equivalent (OCE) system allows HNSCC cells to stratify and invade beyond the basement membrane into underlying connective tissue prepared from decellularized human dermal tissue. The OCE model was inspired by tissue engineering strategies to prepare autologous transplants from human keratinocytes. Advantages of this method over previously used invitro cancer models include the simulation of the basement membrane and complex connective tissue in the construct, in addition to the ability to track the 3D movement of live invading cells and quantify matrix destruction over time. The OCE model and novel live cell imaging strategy may be applied to study other types of 3D tissue constructs.

Abstract 1117: Comprehensive genomic characterization of squamous cell carcinoma of the head and neck in the Cancer Genome Atlas.

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer death in the United States and Worldwide. Most cancers are tobacco-related, although an increasing number of tumors are found in nonsmokers in association with the human papilloma virus (HPV). Methods: The Cancer Genome Atlas (TCGA) is conducting DNA, RNA and miRNA sequencing along with DNA copy number profiling, quantification of mRNA expression, promoter methylation, and reverse-phase protein arrays on surgically resected samples from previously untreated patients with HNSCC. We report for the first time the results for 279 HNSCC samples for whom complete data are available. Results: The demographics of 279 patients enrolled in the study documented a median age of 61 years (range: 19-90); 27% female, and history of tobacco smoking in 80%. Over 30 sites of significant somatic copy number alteration (SCNA) were identified, most of which were shared with recently reported alterations in lung squamous cell carcinoma. However, some notable SCNA were absent in HNSCC: PDGFRA amplification and deletion of FOXP. Similarly, SCNA were compared between HPV + and HPV - tumors identifying numerous differences, including a paucity of receptor tyrosine kinase alterations in HPV + tumors and novel deletions in chromosome 11q and 14q. Exome sequencing revealed at least 15 significantly mutated genes at the False Discovery Rate (FDR) of <0.01, including: CDKN2A, TP53, PIK3CA, FAT1, MLL2, TGFBR2, HLA-A, NOTCH1, HRAS, NFE2L2, and CASP8. Consideration of differences between HPV + and HPV - tumors suggested differences which included nearly universal alteration of TP53 and frequent p16 mutations in HPV - tumors. By contrast, few TP53 or CDKN2A mutations were observed in HPV + samples. Strikingly, a large number of co-occurring genomic alterations were observed. For example, mutations of HRAS were observed nearly universally in combination with either CASP8 or FAT1. All three of these mutations were absent in HPV + patients. mRNA expression profiling revealed four distinct expression subtypes, each one enriched with distinct SCNA and mutational profiles: classical, basal, mesenchymal, and atypical. Deep sequencing by multiple platforms allowed for a detailed accounting of the role of HPV in alterations of the cancer genomes of HNSCC patients, including integration sites, disruption of tumor suppressor genes, and more complex rearrangements. Potential therapeutic targets for clinical trials with currently available drugs will be discussed. Conclusions: HNSCC is a heterogeneous tumor which displays distinctive patterns of somatic alteration potentially amenable to molecularly targeted therapies. We document for the first time using TCGA data, the role of an oncogenic virus in the human cancer genome. Results presented on behalf of TCGA. Citation Format: David N. Hayes, Jennifer Grandis, Adel K. El-Naggar. Comprehensive genomic characterization of squamous cell carcinoma of the head and neck in the Cancer Genome Atlas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1117. doi:10.1158/1538-7445.AM2013-1117

Reflectance Confocal Microscopy - Real-Time In Vivo Imaging of Basal and Squamous Cell Carcinomas

Reflectance and confocal microscopy (RCM) is an in vivo non-invasive imaging tool that captures horizontal images of the epidermis and superficial dermis at nearly the same resolution of routine histopathology. Due to the overlying superficial scaling, RCM characterization of squamous cell carcinomas (SCCs) and associated keratinizing tumors is difficult to visualize due to the obscure appearance of underlying structures. To date, although an increasing frequency of abnormal RCM features are observed across the spectrum, only a few authors have described the features of SCCs. One recent study suggested a disarranged and atypical honeycomb pattern along with round nucleated cells within the spinous/granular layers and round vessels traversing through dermal papilla as key features of SCC. Meanwhile several RCM features have been linked to basal cell carcinomas (BCCs) regardless of type including: Variable architectural disarray of the epidermis A uniform pattern of elongated monomorphic nuclei polarized along the same axis Abundant vessels with prominent tortuosity Mononuclear inflammatory infiltrate admixed with carcinoid basal cells Tightly packed cells in the papillary dermis with a nodular/cord-like growth pattern Palisading tumor cell nuclei Peri-tumoral dark cleft-like spaces representing mucinous edema The presence of bright dendritic cells and melanophages in pigmented BCC Our objective is to identify and describe characteristic RCM findings of SCCs and BCCs by imaging biopsy-proven lesions and reviewing the most recent literature. We will also explain how these features may facilitate diagnosis and recognize future trends for research. Applications of RCM criteria concerning surgical management of these lesions will also be discussed.

Comprehensive genomic characterization of squamous cell carcinoma of the lung.

7006 Background: A third of patients with non-small cell lung cancer are diagnosed with squamous cell carcinoma (SCC) histology. This report describes findings from the comprehensive genomic analyses of 178 SCC samples. Methods: The Cancer Genome Atlas (TCGA) is conducting DNA, RNA, and miRNA sequencing along with DNA copy number profiling, quantification of mRNA expression and promoter methylation on surgically resected samples from previously untreated patients with stage I-III SCC of the lung. Results: The demographics of 178 patients enrolled in the study: median age 68 years (range: 40-85); female 47 (26%) and history of tobacco smoking 171 (96%). Over 30 sites of significant somatic copy number alteration (SCNA) were identified. Exome sequencing of 178 lung SCC and matched normal samples revealed 13 significantly mutated genes with a False Discovery Rate (FDR) of <0.01 and high expression levels, including TP53, CDKN2A, PTEN, KEAP1, and NFE2L2. Apart from the near universal loss of TP53 and CDKN2A, alterations in the NFE2L2/KEAP1 and PI3K/AKT pathways were found in 35% and 43% of tumors analyzed. mRNA expression profiling revealed four distinct expression subtypes, each one enriched with distinct mutations and SCNAs - classical (37%): NFE2L2 and KEAP1 mutations, FGFR kinase alterations, increased global methylation and the highest rate of tobacco use; basal (24%): alterations in FGFR kinases; secretory (24%): PDGFRA alterations; primitive (15%): RB1 mutations. Rearrangements involving several known tumor suppressors were detected by whole genome shotgun sequencing of 20 tumor/normal pairs and confirmed by RNA sequencing including PTEN, RB1, NOTCH1, NF1 and CDKN2A. CDKN2A loss by one of several mechanisms (deletion, mutation, rearrangement with loss of function and methylation) was observed in 72% of specimens. Potential therapeutic targets for clinical trials with currently available drugs were identified in 127 patients (75%). Conclusions: SCC of the lung is a distinct molecular subtype of lung cancer potentially amenable to distinct molecularly targeted therapies.

Molecular cytogenetic characterization of squamous cell carcinoma of the head and neck region

Molecular cytogenetic characterization of squamous cell carcinoma of the head and neck region

Flow Cytometry and Squamous Cell Carcinoma of the Maxillary Sinus: A Possible Prognostic Indicator for Multimodality Intervention

Malignant tumors of the paranasal sinuses constitute less than 1% of all malignancies. Unfortunately, few prognostic factors have been identified regarding the efficacy of interventional therapy. Patients with carcinoma of the maxillary sinus frequently present with an advanced stage of disease and multimodality therapy is often proposed. Although some tumors appear to be more sensitive to preoperative chemotherapy and radiation therapy, a method of predicting and evaluating tumor behavior has not been recognized. Introduced as a means of identifying cell populations with abnormalities in total DNA content, flow-cytometric DNA analysis provides a quick and reliable means of tumor characterization for many malignancies. Although nuclear DNA content has been implicated as a prognostic factor in an increasing number of tumor types, current data on the role of DNA content in head and neck carcinoma is conflicting and incomplete. To evaluate the role of flow-cytometric DNA analysis in predicting therapeutic alternatives, 22 patients with squamous cell carcinoma of the maxillary sinus were reviewed. Patient outcome and histopathologic grade were retrospectively compared with flow-cytometric evaluations of paraffin-embedded formalin-fixed tumor specimens. Four of sixteen tumors (25%) were found to be aneuploid and were also associated with an increased survival rate (p < 0.01). This initial data emphasizes the possible usefulness of DNA measurement for characterization of squamous cell carcinoma of the maxillary sinus and stresses the need for further evaluation.

On characterization of squamous cell carcinoma related antigen from skin and serum of psoriatic patients

On characterization of squamous cell carcinoma related antigen from skin and serum of psoriatic patients

The characterization of squamous cell carcinoma induced by ultraviolet irradiation in hairless mice

Squamous cell carcinomas (SCCs) induced by ultraviolet irradiation in hairless mice were characterized according to their growth, gross appearance and light and transmission electron microscopic features. SCCs arose directly from irradiated skin (ab initio) or progressed from pre-existing epidermal tumours and lesions. SCCs could be graded using guidelines established for human tumours. SCCs comprised 60.8% of the tumours examined. Of these, 35.6% were designated as grade 1, 27.7% as grade 2, 7.9% as grade 3 and 28.7% as grade 4. Spindle cell tumours suspected of being SCCs were included in grade 4. Grades 1, 2 and 3 could not be distinguished on the basis of growth and gross appearance. Those arising ab initio presented as either red, ulcerated lesions or as raised, white, verrucose lesions. Grade 4 SCCs that arose ab initio presented as rapidly growing, red, spherical lesions. Those that arose from pre-existing tumours or lesions had no characteristic appearance, and variable growth. Light microscopically, grade 4 SCCs with an obvious point of origin from epidermis or other epidermal tumours, and putative grade 4 SCCs without such a point of origin, were characterized commonly by spindle cells, pleomorphic giant or multinucleated cells and individual cell reticular fibres. Ultrastructurally, spindle cells, although poorly differentiated, were distinct from flibroblastic proliferations and had few tonofilaments or desmosomes, and were inconsistently surrounded by basal lamina-like material. On the basis of these characteristics, and despite inconclusive positivity with immunoperoxidase staining for keratin and prekeratin, it was concluded that these spindle cell tumours were most probably of identical squamous cell origin.(ABSTRACT TRUNCATED AT 250 WORDS)