Primary Squamous Cell Research Articles

Primary Intraosseous Squamous Cell Carcinoma Arising from Keratocystic Odontogenic Tumor

Primary intraosseous squamous cell carcinoma (PIOSCC) developing from a Keratocystic odontogenic tumor (KCOT) is a rare malignant neoplasm of the jaws. The incidence of carcinomas arising in odontogenic cysts are less. This article presents a case of PIOSCC of the mandible developing from a KCOT in a 35-year-old male patient.

Comparison of performance profiles of TTF1 antibodies for differential diagnosis

Aim Thyroid transcription factor -1 (TTF1) is a useful immunohistochemical (IHC) marker for diagnosis of primary lung tumours including differential diagnosis between primary lung adenocarcinoma (AdCa) and mesothelioma (MM). Different TTF1 monoclonal antibodies (MoAbs) are available. The clone SP141 achieved the highest score in the 2014 RCPA QAP. Most published studies used the 8G7G3/1 MoAb and inconsistencies in labelling between different antibodies have been described. Our study compared the performance of 8G7G3/1 and SP141 TTF1 MoAbs in primary AdCa and squamous cell carcinoma (SCC) of lung, and MM. Methods We examined IHC labelling in 83 cases of MM (17 sarcomatoid, 66 epithelioid), 13 poorly differentiated SCCs and 35 AdCas. Results All AdCas labelled with both the SP141 and 8G7G3/1 MoAbs. All MMs and SCCs were negative with 8G7G3/1, but 7/17 sarcomatoid, 0/66 epithelioid MMs and 6/13 SCCs were positive with SP141. Discussion TTF1 expression is useful for diagnosis of primary lung AdCas, but different antibodies have different performance profiles, which may have clinical implications and must be taken into account.

Primary renal squamous cell carcinoma: a case report

Primary renal squamous cell carcinoma: a case report

Abstract 3019: Aberrant NF-κB and Notch pathways promote CD133+ cancer stem cells in human primary cutaneous squamous cell carcinoma

Abstract The cancer stem cell (CSC) subpopulation has been implicated in inducing tumorigenesis and drug resistance, however, the unique gene program and regulatory signaling that contribute to the CSC phenotypes in human cutaneous squamous cell carcinoma (hcSCC) have not been defined. In this study, a newly improved cell sorting method was developed using a panel of multiple cell surface markers to isolate the small percentage of CD133+ cell population enriched for CSC in primary hcSCC specimens. These cells exhibited CSC features including enhanced spheroid formation in vitro and tumor formation in vivo. Distinct gene expression signatures of the CD133+ subset were profiled by comparing CD133+ CSC with CD133- cancer cells using microarray, which revealed that CD133+ cells expressed enriched stem cell and cancer-related gene programs. In the CD133+ subset, 80 differentially expressed stem cell genes were identified, with an additional set of 69 altered genes enriched in key regulatory pathways, including Notch, NF-κB, Wnt, EMT, and STAT signaling, using Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA). The expression patterns of combined signature genes of CSC and the key regulatory pathways were validated with Nanostring gene expression assay in independent tumor samples. Notch and NF-κB signaling emerged as important pathways. Inhibitors or siRNA knockdown of Notch1/2 and IKKα inhibited NF-κB activity and altered CSC phenotypes, including percentage of CD133+ cells, colony and spheroid formation. Elevated NF-κB signaling was observed in CSCs in the tumor tissues, where immunofluorescent staining showed co-localization of CD133+ and molecules of NF-κB pathway in SCC tumor specimens. Our data support the importance of aberrant NF-κB and Notch signaling in promoting CSC gene program and biologic functions, which could represent predictive diagnostic and prognostic parameters and potential targets for skin cancer prevention and treatment. Supported by NIDCD intramural projects ZIA-DC-000016, 73 and 74. Citation Format: Xinxin Quan, Nga Voong, Weiping Chen, Jamie Coupar, Steven Lee, David W. Petersen, Daniel C. Edelman, Paul S. Meltzer, Andrew Montemarano, Martin Braun, Jonathan Vogel, Carter Van Waes, Zhong Chen. Aberrant NF-κB and Notch pathways promote CD133+ cancer stem cells in human primary cutaneous squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3019. doi:10.1158/1538-7445.AM2014-3019

Abstract 3836: TNFAIP8 protein expression in normal, inflammatory and neoplastic pancreatic tissues: Correlation with endocrine phenotype and advanced stage in ductal adenocarcinomas

Abstract Background: Tumor necrosis factor alpha induced protein 8 (TNFAIP8) is a transcription factor NF-kB inducible antiapoptotic and oncogenic molecule. This gene was initially discovered by comparison of expression profiles of primary and metastatic head and neck squamous cell carcinoma (hence earlier referred to as SCC-S2). Positive correlation between TNFAIP8 expression and cancer progression/poor prognosis has been suggested in a few human solid cancers including pancreatic and esophageal primaries. We were the first to publish the adverse prognostic implication of TNFAIP8 expression in prostatic adenocarcinomas. In this study, we evaluated the significance of this protein in normal, inflamed and neoplastic pancreatic tissues. Design: A total of 184 formalin-fixed, paraffin-embedded pancreatic tissues were analyzed; 151 samples in tissue microarray format [79 primary ductal carcinomas (PDC), 5 ductal adenocarcinomas from distant metastatic sites not matched to primary tumors (MDAC), 9 islet cell tumors (ICT) (one carcinoma), 2 chronic pancreatitis (CP), 29 normal adjacent to cancer, 8 normal adjacent to inflammation, and 19 normal pancreatic tissues] and 19 primary tumor resections [19 primary ductal adenocarcinomas (PDAC), 14 of these with normal tissue adjacent to the cancer]. All samples were immunostained by a manual method using a custom made anti-TNFAIP8 antibody as described earlier (Zhang et al., Int J Cancer, 133: 31-42, 2013). The staining pattern was semiquantitatively assessed based on staining intensity and distribution and the results were correlated with clinicopathologic variables. Results: Immunoreactivity for TNFAIP8 was predominantly cytoplasmic. TNFAIP8 protein overexpression was noted in 44/184 (24%) samples and correlated with tumor type [9/98 (9%) PDC/PDAC 2/5 (40%) unmatched distant MDAC, 5/9 (56%) (ICT) (1/1 carcinoma), 1/2 (50%) (CP), 15/43 (35%) normal adjacent to cancer, 5/8 (63%) normal adjacent to inflammation, and 7/19 (37%) normal pancreatic tissues, p<0.0001], with advanced tumor stage within PDC/PDAC [0/24 (0%) Stage I vs 3/44 (7%) Stage II vs 6/23 (26%) Stage III vs 0/7 (0%) Stage IV, p=0.010], and overall with gender [34/107 (32%) male vs 10/77 (13%) female, p=0.003]. Islets were present in 63 cases, all (100%) showing TNFAIP8 protein overexpression. Conclusion: TNFAIP8 immunohistochemical expression correlates with endocrine phenotype and portends poor prognosis in pancreatic ductal carcinomas. This protein may represent both a novel pathway in endocrine differentiation and a therapeutic target in the management of aggressive PDC, warranting further study. Citation Format: Jeffrey S. Ross, Bhaskar VS Kallakury, Hwa Jeong Lee, David M. Jones, Sanaz Ainechi, Gregory M. Sheehan, Christine E. Sheehan, Usha N. Kasid. TNFAIP8 protein expression in normal, inflammatory and neoplastic pancreatic tissues: Correlation with endocrine phenotype and advanced stage in ductal adenocarcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3836. doi:10.1158/1538-7445.AM2014-3836

Abstract 1422: Validation of primary non-small cell lung cancer model: Stable isotope-resolved metabolomics (SIRM) reveals functional biochemistry

Abstract Stable isotope-resolved metabolomics (SIRM) provides a comprehensive and functional readout of cellular activity and is therefore a useful tool both for biomarker discovery and fundamental cancer biology. We have established a primary lung squamous cell carcinoma line (PSLC1), isolated from the lung tumor tissue of a non-small cell lung cancer patient, for which the metabolic profile has been established. We used SIRM to characterize the metabolic activity of the cells in mouse xenografts and in cell culture. Here we report the metabolic activities of the cell line in culture using two different tracers to evaluate central metabolism. PSLC1 cells were grown in either [U-13C]-glucose or [U-13C,15N]-glutamine labeled medium. Cell extracts and medium were prepared and analyzed by 1H-NMR, HSQC, TOCSY, GC-MS, and FTICR-MS. Cells exhibited linear glucose consumption that persisted even as proliferation plateaued. The conversion of glucose to lactate occurred at a strikingly high 89%. Anaplerotic pathways involving pyruvate carboxylation and glutaminolysis were active and appeared to be dependent on cellular proliferation. Glutamine represented an important contributor for biosynthetic and bioenergetic cellular needs, including de novo pyrimidine biosynthesis and glucose-independent TCA cycling. In addition, glutamine served as the major precursor in proline and glutathione biosynthesis. Distinct glutamine utilization and labeling patterns indicated that this cancer might be driven by C-MYC overexpression. C-MYC overexpression was observed by targeted protein analysis guided by metabolomics-edited transcriptomics analysis (Pro-META). The ability of SIRM to generate hypotheses about protein expression demonstrates its potential use as a first line biomarker detection method. Comparison with upstream in situ and xenograft data will allow us to assess model validity and the effects of tumor microenvironment. In turn, the in vitro data will help us interpret human in situ data more robustly. Supported by grant R25-CA-134283 and 1P01CA163223-01A1 from the National Cancer Institute Citation Format: Connor J. Kinslow, Teresa W-M Fan, Jin L. Tan, Pawel K. Lorkiewicz, Ramya Balasubramaniam, Yihua Cai, Jun Yan, Andrew N. Lane. Validation of primary non-small cell lung cancer model: Stable isotope-resolved metabolomics (SIRM) reveals functional biochemistry. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1422. doi:10.1158/1538-7445.AM2014-1422

Abstract 1525: Exome sequencing to identify permissive mutations representing acquired vulnerabilities in lung cancer

Abstract When a lung epithelial cell acquires a driver mutation (e.g. in KRAS) it often needs to acquire additional ‘permissive’ genetic alterations to enable the cell to tolerate the oncogenic change. These ‘permissive' alterations represent an ‘acquired vulnerability' and consequently a novel therapeutic target in lung cancers driven by known, but currently un-targetable, driver mutations. Immortalized Human Bronchial Epithelial Cells (HBECs) represent a cell appropriate in vitro model to study the origin and pathogenesis of lung cancer following introduction of defined oncogenic changes. We have previously transformed HBECs to full malignancy by introducing five genetic manipulations (to CDK4, TERT, TP53, KRAS, MYC, BCL2, PTEN and/or STK11). While malignant transformation will be largely driven by the exogenous oncogenotype -i.e. the introduced oncogenic alterations- we hypothesize the cells also must undergo additional somatic ‘permissive' changes to bypass anti-tumor mechanisms. While lung cancers are often highly mutated (mainly due to carcinogens in cigarette smoke), manipulated HBECs should exhibit fewer somatic mutations, providing greater power to identify important somatically acquired mutations that facilitate tumorigenic progression of lung epithelial cells. We have sequenced the exomes of a series of 22 genetically manipulated HBECs derived from two individuals and representing 15 unique oncogenotypes (combinations of 3-5 introduced manipulations). Paired-end sequencing was performed with an Illumina HiSeq 2000 using a VCRome 2.1 liquid capture design ‘exome chip’. The median fold coverage was 114X, resulting in at least 90% of targeted bases are covered at >20-fold. Somatic mutations were called by comparing manipulated HBECs to their immortalized parental cell line. Manipulated HBECs had a median somatic mutation rate of 0.92 mutations/Mb, 7-9-fold lower than observed in lung cancers and tumor cell lines. The median mutation rate increased with the number of introduced manipulations (HBECs with three, four and five manipulations had 0.47, 0.97 and 0.92 mutations/Mb, respectively). Non-synonymous somatic mutations were identified in 470 genes. Thirty-nine genes were mutated in ≥3 HBECs (recurrent mutations) and of these, 35 genes (none currently regarded as ‘driver’ oncogenes and 5 potentially ‘druggable' [DGIdb]) were also mutated in primary lung adenocarcinoma and squamous cell carcinomas (TCGA data). We found the introduction of defined oncogenic alterations in HBECs is accompanied by the acquisition of somatic mutations. Leveraging against public somatic mutation data for lung tumors has allowed us to prioritize mutations for follow up to better identify potential acquired vulnerabilities in lung cancer cells and therefore, novel therapeutic targets. Citation Format: Jill E. Larsen, Caleb F. Davis, Kenneth Huffman, Luc Girard, David A. Wheeler, Richard A. Gibbs, John D. Minna. Exome sequencing to identify permissive mutations representing acquired vulnerabilities in lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1525. doi:10.1158/1538-7445.AM2014-1525

Abstract 985: The mutational landscape of LN metastasis and recurrence in HNSCC

Abstract Recent whole exome sequencing (WES) studies have reported the mutations that characterize primary head and neck squamous cell carcinomas (HNSCC). While exposure to tobacco, alcohol and HPV infection are known to contribute to HNSCC development and prognosis, the largest obstacle to long term survival is recurrent and metastatic disease. Approximately 50% of patients present with synchronous lymph node metastases (SLNM), where 5-year adjusted survival is ≈85% for patients without SLNM compared with 30-60% in patients with SLNM. 20-30% of patients cured of their primary HNSCC go on to develop recurrent disease, which is usually refractory to standard therapies. Here, we report the first WES study of paired primary tumor and SLNM from 14 HNSCC patients, and paired primary tumor and metachronous loco-regional metastases (MLRM) from 11 HNSCC patients. Primary tumors averaged 67 nonsynonymous mutations per tumor (n=21), SLNM averaged 89.3 (n=12), and MLRM averaged 41.7 (n=9). TP53 was the only gene mutated in a majority (57%) of primary tumors in our cohort. We observed similar rates of mutation in several of the TCGA-defined “HNSCC signature” genes in our primary cohort, including FAT1 (14.3%) and CASP8 (4.8%), among others. While the size of our cohort does not allow for appropriately powered statistical analyses; 206 and 204 genes, were mutated in metastatic tumors, but not the respective paired primary tumors, in the SLNM and MLRM cohorts, respectively. AP2B1 and ITPR3 mutations were enriched in SLNM, as newly acquired mutations were seen in multiple (2 and 2/12) SLNM samples. GLUL and DDR2 mutations were enriched in MLRM, as newly acquired mutations were seen in multiple (2 and 2/9) MLRM samples. All 4 genes have previously been implicated in the metastatic process in other cancers. The potential enrichment of DDR2 mutations in HNSCC metastases is especially intriguing, as mutations in this gene have been shown to confer sensitivity to the SRC-family kinase inhibitor, dasatinib, in lung and breast cancer. Here we report exquisite sensitivity to dasatinib in our HNSCC preclinical models harboring DDR2 mutations, suggesting further investigation of this drug is warranted in recurrent HNSCC. Citation Format: Matthew Louis Hedberg, Gerald Goh, Maria Freilino, Yan Zeng, Vivian WY Lui, Roy S. Herbst, Richard P. Lifton, Jennifer R. Grandis. The mutational landscape of LN metastasis and recurrence in HNSCC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 985. doi:10.1158/1538-7445.AM2014-985

Predictive value of SUV-based parameters derived from pre-treatment (18)F-FLT PET/CT for short-term outcome with head and neck cancers.

The aim of this study was to investigate the predictive potential of pre-treatment 3'-deoxy-3'-[18F]-fluorothymidine (FLT) uptake parameters for short-term outcome of primary head and neck squamous cell cancer (HNSCC) patients. A total of 32 patients undergoing pre-treatment FLT positron emission tomography/computed tomography (PET/CT) from May 2010 to May 2013 were evaluated. Semi-quantitative assessment was used to determine mean, peak and maximum standardized uptake values (SUVmean, SUVpeak and SUVmax), metabolic tumor volume (MTV) and total lesion proliferation (TLP). Clinicopathologic factors and PET/CT parameters were analyzed for their association with 2-year loco-regional control (LRC) and overall survival (OS). The mean (±SD) SUVmean, SUVpeak, SUVmax, MTV and TLP were 5.97±3.16, 6.71±3.75, 10.05±5.37, 7.31±8.05 and 44.95±52.82, respectively. In univariate analyses, N category was associated with OS (P=0.037). Increased MTV ≥13ml was associated with decreased LRC and OS (P<0.0001). TLP ≥69.3g was also linked with both LRC and OS (P=0.009 and 0.015, respectively). Regarding SUVs, only the SUVpeak was associated with LRC and OS (P=0.035 and 0.049, respectively). Pre-treatment MTV is the most useful parameter with FLT PET/CT. TLP and SUVpeak may also provide important prognostic information for patients with HNSCCs.

Invasive pulmonary aspergillosis: A rare complication after microwave ablation

Three cases are reported of invasive pulmonary aspergillosis (IPA) occurring after microwave ablation (MWA) for lung tumours. This is a rare complication that has not previously been described in the literature. The diagnosis of IPA was based on the following factors: host factors, clinical manifestations and mycological findings. The first case was a 63-year-old man treated for primary lung squamous carcinoma. Significant tumour regression was achieved by 18 days after MWA, medical treatment with itraconazole for 6 weeks, and postural drainage. The second case, a 65-year-old man, was confirmed with primary lung squamous cell carcinoma. Voriconazole administration using intravenous infusion combined with intracavitary lavage was therapeutically effective after MWA at 1 year follow-up. The third case was a 61-year-old woman with primary lung adenocarcinoma. Delayed pneumothorax and bronchopleural fistula secondary to IPA persisted. The patient died from secondary multiple organ function failure. Despite its very low incidence, the significance of early diagnosis and early administration of antifungal therapy should be highlighted because of the relentless severity of IPA in patients undergoing MWA.

Novel Biomarkers to Discriminate Between Primary Lung Squamous Cell Carcinoma and Adenocarcinoma Identified By the Cap Analysis of Gene Expression (Cage) Method

ABSTRACT Aim: In recent years, the use of targeted therapies focused on the molecular and histological features of cancer types has entered standard practice. In the context of non-small cell lung cancers, it is necessary to discriminate between squamous cell carcinoma (Sq) and adenocarcinoma (Ad) in order to select the most effective treatment regimen. However, this is sometime challenging to the pathologist in small biopsy specimens, especially for distinguishing poorly differentiated (P/D) Sq from Ad without a lepidic growth component (BAC). Methods: Cap Analysis of Gene Expression (CAGE) is a method that can be used to quantify the transcription initiation reflecting the gene expression levels across the whole genome by determining the 5' ends of capped RNA molecules using high-throughput sequencers. We performed CAGE on 97 frozen tumor tissue samples of surgically resected lung cancers (Sq, N = 22; Ad, N = 75), including P/D Sq and Ad without BAC. We subsequently explored whether there were novel biomarkers that could be used to discriminate the two types of cancers. Results: (1) We confirmed that the expression levels of existing molecular markers used in the immunohistochemical (IHC) analysis of Sq (CK5, CK6, p40 and desmoglein-3) and Ad (TTF-1 and napsin A) were significantly different between P/D Sq (N = 3) and Ad without BAC (N = 12) in our CAGE data, but the performance to discriminate the two types of cancers were insufficient. (2) We identified four novel biomarkers, consisting of two protein coding genes and two non-coding RNAs, which showed better performance for discrimination than the existing markers. (3) Of the two protein coding genes, the expression level of SPATS2 was higher in Sq than in Ad, regardless of the extent of tumor differentiation. (4) The expression level of ST6GALNAC1, the other protein coding gene, was higher in Ad than in Sq, regardless of the presence of BAC. Conclusions: We identified four biomarkers, including SPATS2 and ST6GALNAC1, protein coding genes, which may be useful to discriminate Sq from Ad by using CAGE. While further validation will be needed, our data indicated the performance of these markers to discriminate Sq from Ad is superior to that of the existing markers, leading to the more accurate selection of targeted therapies for non-small cell lung cancers. Disclosure: All authors have declared no conflicts of interest.

Epidermotropic metastatic epithelioid sarcoma: a potential diagnostic pitfall

Epithelioid sarcoma (ES) represents an aggressive soft tissue tumor with varied morphologic and histopathologic presentations that typically elicits a broad differential diagnosis, including granuloma annulare, necrobiotic granuloma, fibrous histiocytoma, synovial sarcoma, amelanotic melanoma and poorly differentiated primary cutaneous and metastatic adenocarcinoma. ES is characterized microscopically by a nodular arrangement of abundant, deeply eosinophilic, polygonal tumor cells with frequent central necrosis and hemorrhage, rare mitotic figures and minimal pleomorphism. At the periphery, tumor cells are spindle shaped and may exhibit frequent local infiltration along tendons, fascial planes and neurovascular bundles. Immunohistochemistry typically reveals expression of both epithelial and mesenchymal antigens, such as cytokeratin and vimentin, respectively. The absence of a connection between tumor cells and the overlying epidermis, with or without an in situ carcinoma component, typically rules out a primary cutaneous squamous cell carcinoma. We report a case of stage IV proximal-type ES that mimicked molluscum contagiosum clinically and was histopathologically reminiscent of invasive squamous cell carcinoma because of attachment and colonization of the overlying epidermis. The case represents an unusual pathologic presentation of ES and highlights potential pitfalls in establishing the diagnosis.

520 Unconjugated but Not Conjugated Bile Acid Reduces Squamous Differentiation in Esophageal Cells Possibly Through Intracellular Mechanisms

Background: Barrett's Esophagus (BE) is a precancerous lesion in which the normal squamous epithelium of the esophagus undergoes columnar metaplasia as a result of protracted duodeno-esophageal reflux. Bile acid (BA) both conjugated and unconjugated at an acidic pH, forms the chief component of reflux and has the ability to affect cellular processes by virtue of its anionic detergent action or acting as a signaling molecule. Previously, our group had shown that the esophageal squamous epithelium loses the expression of genes involved in squamous differentiation following exposure to a cocktail containing conjugated and unconjugated BA at pH5. In this study, we aimed determining which BA component, whether conjugated or unconjugated, predominantly contributed to the down-regulation of squamous differentiation. Methods: Human telomerase-immortalized primary esophageal squamous cells (EPC1) were grown on polyester transwells and treated separately with conjugated or unconjugated BA at both pH7.4 and pH5, in 15 min pulses three times a day for six days. Trans-epithelial Electrical Resistance (TEER) was measured daily, and at the end of the treatment cells were harvested for mRNA and protein. Results: Unconjugated BA at pH5 reduced the expression of genes involved in squamous differentiation as well as the TEER in the EPC1 in transwells culture, whereas conjugated BA did not have any significant effect. Moreover, unconjugated BA at pH5 induced the expression of FGF-19, a transcription target of BA nuclear receptor FXR. Conclusions: Unconjugated BA at pH5 is unionized and can penetrate through cell membrane to enter EPC1 cells. On the other hand, EPC1 cell membrane is impermeable to conjugated BA due to the absence of apical BA transporters. Since the anionic detergent properties of BA increases with conjugation and ionization, these results implicate a possible intracellular signaling mechanism of action of BA to reduce the squamous differentiation in primary esophageal cells, as opposed to detergent action. Long term gastric acid suppression therapy might be putting patients at risk to BA induced altered cellular differentiation, as the therapy is known to increase bacterial deconjugation of BA.

523 Comparison of Hospital Charges Between Laparoscopic Heller Myotomy and POEM

Background: Barrett's Esophagus (BE) is a precancerous lesion in which the normal squamous epithelium of the esophagus undergoes columnar metaplasia as a result of protracted duodeno-esophageal reflux. Bile acid (BA) both conjugated and unconjugated at an acidic pH, forms the chief component of reflux and has the ability to affect cellular processes by virtue of its anionic detergent action or acting as a signaling molecule. Previously, our group had shown that the esophageal squamous epithelium loses the expression of genes involved in squamous differentiation following exposure to a cocktail containing conjugated and unconjugated BA at pH5. In this study, we aimed determining which BA component, whether conjugated or unconjugated, predominantly contributed to the down-regulation of squamous differentiation. Methods: Human telomerase-immortalized primary esophageal squamous cells (EPC1) were grown on polyester transwells and treated separately with conjugated or unconjugated BA at both pH7.4 and pH5, in 15 min pulses three times a day for six days. Trans-epithelial Electrical Resistance (TEER) was measured daily, and at the end of the treatment cells were harvested for mRNA and protein. Results: Unconjugated BA at pH5 reduced the expression of genes involved in squamous differentiation as well as the TEER in the EPC1 in transwells culture, whereas conjugated BA did not have any significant effect. Moreover, unconjugated BA at pH5 induced the expression of FGF-19, a transcription target of BA nuclear receptor FXR. Conclusions: Unconjugated BA at pH5 is unionized and can penetrate through cell membrane to enter EPC1 cells. On the other hand, EPC1 cell membrane is impermeable to conjugated BA due to the absence of apical BA transporters. Since the anionic detergent properties of BA increases with conjugation and ionization, these results implicate a possible intracellular signaling mechanism of action of BA to reduce the squamous differentiation in primary esophageal cells, as opposed to detergent action. Long term gastric acid suppression therapy might be putting patients at risk to BA induced altered cellular differentiation, as the therapy is known to increase bacterial deconjugation of BA.

To what degree is there interobserver variability among pathologists for T1 penile cancer?

381 Background: Molecular and genetic markers have yet to be developed to predict those patients that are at risk for lymph node metastasis. Currently, the grading of penile cancer plays a critical role in the determination of which patients receive an inguinal lymph node dissection (ILND) along with other treatment modalities. We sought out to determine the variance among genitourinary (GU) pathologists at a tertiary cancer center for penile cancer based on a European model. Methods: Nine patients that were diagnosed with stage pT1 primary penile squamous cell carcinoma were selected who underwent either a partial (8) or radical penectomy (1) from 10/2000 to 09/2009. All slides from each case were reviewed by each of the 3 reviewing pathologists, independently, who diagnosed the subtype of squamous cell carcinoma according to WHO criteria, assigned a grade, noted whether lymphovascular invasion was present or not and finally staged the tumor according to the AJCC Cancer Staging Manual, 7th edition. No access to the original, final pathological diagnosis was allowed. Interobserver variance between the 3 GU pathologists and each variable was calculated using Cohen’s kappa coefficient. Results: Complete agreement was reached in 3 cases for tumor grade and 4 cases for tumor stage out of 9. Overall, the 3 GU pathologists only displayed fair agreement at 30% for tumor grade (ê = 0.30, p = 0.018) and trended towards fair agreement at 24% (ê = 0.24, p = 0.077) and 25% (ê = 0.250, p = 0.097) for tumor stage and LVI respectively. Conclusions: The variance displayed herein demonstrates the difficulty in identifying individuals that would benefit from a diagnostic/therapeutic lymph node dissection based on pathological staging. This corroborates that of the European model and calls for novel methods to determine reproducible prognostic markers.

Atypical presentation of primary renal squamous cell cancer : a case report

Renal squamous cell cancer is one of the rare primary urothelial tumors with only a handful of cases reported in literature. Because of high grade, advanced and late presentation, they herald a grave prognosis. They are frequently associated with calculus disease, smoking, phenacetin consumption and foci of squamous metaplasia due to chronic irritation. Nephroureterectomy is the treatment of choice for such tumors. We hereby present a case of 59 year old female who presented with squamous cell cancer of renal pelvis. The case presented here is different from what has already been reported in literature, as the patient had no antecedent risk factors for renal squamous cell carcinoma. ------------------------------------------------- Cite this article as : Pahwa M, Pahwa AR, Girotra M, Chawla A. Atypical presentation of primary renal squamous cell cancer: a case report. Int J Cancer Ther Oncol 2014; 2 (1):02015. DOI: http://dx.doi.org/10.14319/ijcto.0201.5

Atrial Metastatic Tumor: Transthoracic and Transesophageal Echocardiograph Imaging

A 68-year-old male patient was admitted to our hospital because of weakness, dyspnea on exertion and palpitations. Transthoracic and transesophageal echocardiograph revealed a dilated left atrium with an immobile intracavitary mass, without signs of left atrium outflow obstruction. Bronchoscopy was performed and the histopathologic review of the samples obtained was consistent with a primary lung squamous cell carcinoma. J Med Cases. 2014;5(1):15-17 doi: http://dx.doi.org/10.4021/jmc 1390w

A fatal case of primary basaloid squamous cell carcinoma in the intrahepatic bile ducts.

Primary squamous cholangiocellular carcinomas are very rare. We describe a case of a 67-year-old man, who underwent chemotherapy and surgery for a right-sided liver tumor with an unusual presentation of metastasis to a lymph node in the left armpit. The patient was asymptomatic at the time of diagnosis but expired 20 months after surgery with epidural, lung, and spine metastasis. In addition to the unusual clinical presentation, the diagnosis of the liver tumor was that of a primary basaloid squamous cell carcinoma of the intrahepatic bile ducts, an entity with only one previous report in the literature.

In-transit Metastasis from Primary Cutaneous Squamous Cell Carcinoma in a Non-immunosupressed Patient

In-transit Metastasis from Primary Cutaneous Squamous Cell Carcinoma in a Non-immunosupressed Patient

Update of odontogenic tumors

The latest WHO classification of odontogenic tumours was published in 2005. The classification has been used as a global standard for last 10 years but our knowledge of odontogenic tumors continues to evolve. At biennial meetings of International Association of Oral and Maxillofacial pathologists (IAOP), we have started discussions on classification of odontogenic tumors toward the next WHO Classification. I would like to introduce some subjects of discussion including cyst-tumor interface (odontogenic keratocyst vs keratocystic odontogenic tumor, glandular odontogenic cyst vs central mucoepidermoid carcinoma, calcifying odontogenic cyst vs ghost cell lesions); placement of adenomatoid odontogenic tumor (hamartoma vs neoplasia, epithelial tumor vs mixed tumor with dentin formation), clear cell odontogenic carcinoma with dentinoid formation; primary intraosseous squamous cell carcinoma vs sclerosing odontogenic carcinoma; classification based on inductive phenomenon of odontogenesis vs clinical behavior and others. Recent advances in molecular analyses of odontogenic tumors will be presented. I expect to exchange opinions on the new classification of odontogenic tumors.