Biopsy Of Squamous Cell Carcinoma Research Articles

Macrophages of M1 phenotype have properties that influence lung cancer cell progression.

Stromal macrophages of different phenotypes can contribute to the expression of proteins that affects metastasis such as urokinase-type plasminogen activator (uPA), its receptor uPAR, and plasminogen activator inhibitor-1 (PAI-1), but knowledge of how essential their contribution is in comparison to the cancer cells in small cell lung cancer (SCLC) and lung squamous cell carcinoma (SCC) is lacking. The expression of uPA, uPAR, and PAI-1 and of the matrix metalloproteinases (MMP)-2 and MMP-9 were studied in human macrophages of M1 and M2 phenotype and compared to a lung SCC (NCI-H520) and a SCLC (NCI-H69) cell line. Effects of treatment with conditioned media (CM) from M1 and M2 macrophages on the expression of these genes in H520 and H69 cells as well as effects on the cell growth were investigated. In addition, data on the stromal macrophages immunoreactivity of uPAR, MMP-2, and MMP-9 in a few SCC and SCLC biopsies was included. uPAR, MMP-2, and MMP-9 were confirmed in stromal cells including macrophages in the SCC and SCLC biopsies. In vitro, both macrophage phenotypes expressed considerably higher mRNA levels of uPA, uPAR, PAI-1, and MMP-9 compared to the cancer cell lines, and regarding uPAR, the highest level was found in the M1 macrophage phenotype. Furthermore, M1 CM treatment not only induced an upregulation of PAI-1 in both H520 and H69 cells but also inhibited cell growth in both cell lines, giving M1 macrophages both tumor-promoting and tumor-killing potential.

Hypermethylation of promoter region of LATS1--a CDK interacting protein in oral squamous cell carcinomas--a pilot study in India.

Epigenetic silencing of tumor suppressor genes due to promoter hypermethylation is one of the frequent mechanisms observed in cancers. Hypermethylation of several tumor suppressor genes involved in cell cycle regulation has been reported in many types of tumors including oral squamous cell carcinomas. LATS1 (Large Tumor Suppressor, isoform 1) is a novel tumor suppressor gene that regulates cell cycle progression by forming complexes with the cyclin dependent kinase, CDK1. Promoter hypermethylation of the LATS1 gene has been observed in several carcinomas and also has been linked with prognosis. However, the methylation status of LATS1 in oral squamous cell carcinomas is not known. As oral cancer is one of the most prevalent forms of cancer in India, the present study was designed to investigate the methylation status of LATS1 promoter and associate it with histopathological findings in order to determine any associations of the genetic status with stage of differentiation. Tumor chromosomal DNA isolated from biopsy tissues of thirteen oral squamous cell carcinoma biopsy tissues were subjected to digestion with methylation sensitive HpaII enzyme followed by amplification with primers flanking CCGG motifs in promoter region of LATS1 gene. The PCR amplicons were subsequently subjected to agarose gel electrophoresis along with undigested amplification control. HpaII enzyme based methylation sensitive PCR identified LATS1 promoter hypermethylation in seven out of thirteen oral squamous cell carcinoma samples. The identification of LATS1 promoter hypermethylation in seven oral squamous cell carcinoma samples (54%), which included one sample with epithelial dysplasia, two early invasive and one moderately differentiated lesions indicates that the hypermethylation of this gene may be one of the early event during carcinogenesis. To the best of our knowledge, this is the first study to have explored and identified positive association between LATS1 promoter hypermethylation with histopathological features in oral squamous cell carcinomas.

Surgical Excision of Non-Melanoma Skin Cancer in an Elderly Veteran's Affairs Population.

Background:Non–melanoma skin cancer (NMSC) is the most common malignancy in the United States. Recommended treatment for NMSC remains surgical excision following a positive biopsy. Evidence of complete spontaneous regression of residual NMSC exists in the case of small lesions macroscopically removed by shave biopsy, but with a positive microscopic margin. The present study investigates the rate at which residual tumor is present at subsequent excisional biopsy, with the aim to assess if recommendation to forgo surgical excision can be made.Methods:A total of 233 shave biopsies of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) were performed during a 5-year period. All specimens included in the study were less than 2 cm in diameter, were macroscopically removed by shave biopsy, and had a positive initial microscopic margin.Results:On subsequent surgical excisional biopsy, 42% of BCC specimens were negative for residual tumor, 38% had residual tumor, but the tumor was completely contained in the excised specimen, and 20% of the specimens had positive margin residual tumor. For SCC specimens, 73% were negative for residual tumor, 21% had residual tumor, but the tumor was completely contained in the excised specimen, and 6% of the specimens had positive margin residual tumor.Conclusions:Although reduction of residual tumor at reexcision is noted with both BCC and even more so with SCC, the rate at which this occurs is not sufficient that a general recommendation to forgo surgical excision can be made.

Antioxidant Enzyme Levels in Pathogenesis of Oral Squamous Cell Carcinoma (OSCC)

Increased oxidative stress and altered anti-oxidant defense systems have been implicated in the pathogenesis of several diseases including cancer. Therefore, the aim of our study is to evaluate the antioxidant enzyme levels such as superoxide dismutase (SOD) and catalase in blood samples and tissues collected from oral squamous cell carcinoma patients and compared with healthy controls.The collected blood samples and tumor tissues from the diseased individuals and the normal controls are analyzed for malondialdehyde (MDA) and nitric oxide (NO), which is the indicator of oxidative and nitrosative stress respectively. The anti-oxidant enzymes SOD and catalase levels are measured by UV visible spectrophotometer. Subsequently, immuno-histostaining for antioxidant enzymes were performed in oral squamous cell carcinoma biopsies and sections were analyzed.The levels of MDA and NO were significantly elevated in the blood and tissue samples of OSCC patients. The antioxidant enzymes SOD and catalase were significantly reduced in OSCC tissues; while in erythrocytes catalase level is reduced whereas the SOD level is increased. Further, the reduced immuno-histostaining was observed for catalase and SOD in OSCC tissues when compared to normal oral epithelium.The enhanced levels of MDA and NO revealed that increased oxidative stress in conjunction with the reduced antioxidant defense mechanism in OSCC patients, might be involved in cancer progression. Our results suggest that detection of reactive oxygen species (ROS) and antioxidant enzymes levels might be a valuable marker in cancer prognosis and for improving therapeutic strategies in oral cancer.

Retrospective chart review of skin cancer presence in the wide excisions

To investigate cancer cell absence or presence in wide excision after biopsy of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) patients. 200 patients (100 BCC and 100 SCC) from the same dermatology clinic, who had positive margin upon biopsy, were selected from a computer generated randomized report. All selected patients had wide excision following biopsy. To determine the correlation of gender, age distribution and cancer absence, BCC and SCC cases were separated based on excision-cancer absent or present after wide excision. χ(2) tests, Fisher's exact tests were used to analyze the ratio of male to female between excision-cancer absent and excision-cancer present patients, while Mann-Whitney U test were used to compare the age distribution in the two groups. Statistical analyses were performed using SPSS version 16.0 for Windows. Our retrospective chart review of the patients showed that cancer cells were absent in 49% of BCC patients (n = 100) and 64% of SCC patients (n = 100) who had previously had positive margins upon biopsy. Gender analysis showed the ratio of male to female (M/F) in the BCC arm was significantly higher compared with the SCC arm in those with excision-cancer absent (2.06 vs 0.66; P = 0.004; χ(2) test). But M/F of excision-cancer absent and excision-cancer present in neither BCC nor SCC patients was statistically significant. Age adjustment showed no significant difference between excision-cancer absent and excision-cancer present in BCC and SCC patients. Nevertheless, in excision-cancer absent cases, the age distribution showed that the BCC patients were younger than SCC patients (average age 67 vs 74; P < 0.001; Mann-Whitney U test). In addition, our data also indicated that in the patient group of 71-80 years old, there were more SCC patients who showed excision-cancer absence (67.6% vs 39.4%; P = 0.02; χ(2) test). Our study indicates that approximately 50% or more of BCC and SCC patients with positive margins found on biopsies did not have cancer cells present at the time of wide excisions.

Comprehensive analysis of HPV expression in laryngeal squamous cell carcinoma.

Role of human papillomavirus (HPV) in laryngeal carcinoma remains controversial. The aim of this study is to evaluate the role of HPV in laryngeal squamous cell carcinoma by determining presence of markers of viral infection. HPV DNA and E6*I mRNA status was determined by type-specific E7 PCR bead-based multiplex genotyping and RT-PCR assays in laryngeal squamous cell carcinoma biopsy samples. p16(INK4a) and COX-2 expression was determined by immunohistochemistry. Four cases out of 32 (13%) were HPV DNA+: HPV 11 (n = 1), HPV 31 (n = 3), HPV 59 (n = 1). One double infection: HPV 11 and HPV 31. p16(INK4a) was overexpressed in three cases (9%) and COX-2 in 17 cases (53%). Two of four HPV DNA+ samples had E6*I mRNA for HPV 31 and overexpressed p16(INK4a) and COX-2. HPV appears to play an active role in a small subset of laryngeal squamous cell carcinoma. p16(INK4a) can be used as a surrogate marker of transcriptionally active HPV infection; COX-2 expression had no correlation with HPV DNA and/or RNA positivity.

Loss of TAK1 increases cell traction force in a ROS-dependent manner to drive epithelial–mesenchymal transition of cancer cells

Epithelial–mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFβ–SMAD signaling pathway as an inductor of EMT in many tumor types is well recognized. However, the role of non-canonical TGFβ–TAK1 signaling in EMT remains unclear. Herein, we show that TAK1 deficiency drives metastatic skin squamous cell carcinoma earlier into EMT that is conditional on the elevated cellular ROS level. The expression of TAK1 is consistently reduced in invasive squamous cell carcinoma biopsies. Tumors derived from TAK1-deficient cells also exhibited pronounced invasive morphology. TAK1-deficient cancer cells adopt a more mesenchymal morphology characterized by higher number of focal adhesions, increase surface expression of integrin α5β1 and active Rac1. Notably, these mutant cells exert an increased cell traction force, an early cellular response during TGFβ1-induced EMT. The mRNA level of ZEB1 and SNAIL, transcription factors associated with mesenchymal phenotype is also upregulated in TAK1-deficient cancer cells compared with control cancer cells. We further show that TAK1 modulates Rac1 and RhoA GTPases activities via a redox-dependent downregulation of RhoA by Rac1, which involves the oxidative modification of low-molecular weight protein tyrosine phosphatase. Importantly, the treatment of TAK1-deficient cancer cells with Y27632, a selective inhibitor of Rho-associated protein kinase and antioxidant N-acetylcysteine augment and hinders EMT, respectively. Our findings suggest that a dysregulated balance in the activation of TGFβ–TAK1 and TGFβ–SMAD pathways is pivotal for TGFβ1-induced EMT. Thus, TAK1 deficiency in metastatic cancer cells increases integrin:Rac-induced ROS, which negatively regulated Rho by LMW-PTP to accelerate EMT.

Assessment of Laminin-5 in Oral Dysplasia and Squamous Cell Carcinoma

Laminin-5 is an important protein in the establishment of an intact basement membrane. The aims of this study were to assess the expression of laminin-5 (γ2 chain) using cyclin D1 and Ki-67 in hyperplastic oral mucosal lesions, oral dysplasia, and squamous cell carcinoma (SCC). Paraffin-embedded tissue blocks of 134 patients were stained for laminin-5, cyclin D1, and Ki-67 using immunohistochemistry and assessed by virtual microscopy. Statistical analysis was performed using Kruskal-Wallis tests and Mann-Whitney U tests for post hoc assessment. Laminin-5, cyclin D1, and Ki-67 were found to have significant differences in expression for the different categories of dysplasia, SCC, and hyperplasia (P < .001). Cyclin D1 and Ki-67 expression levels were significantly increased in moderate and severe dysplasia and SCC, with no significant difference in expression between hyperplasia and mild dysplasia or between biopsies of severe dysplasia and SCC. Laminin-5 expression was only significantly increased in SCC, confirming it as a marker of malignant transformation and invasion. The results of this study indicate that overexpression of laminin-5 is found only in SCC and not dysplastic lesions. Therefore, laminin-5 has potential as a marker for the intraoperative assessment of cancer excision margins and could be used as a target for chemotherapeutic agents.

Interferon Stimulated Gene - ISG15 is a Potential Diagnostic Biomarker in Oral Squamous Cell Carcinomas

Cancer diagnostic biomarkers have a wide range of applications that include early detection of oral precancerous lesions and oral squamous cell carcinomas, and assessing the metastatic status of lesions. The interferon stimulated ISG15 gene encodes an ubiquitin-like protein, which conjugates to stabilize activation status of associated proteins. Hence a deregulated expression of ISG15 may promote carcinogenesis. Indeed overexpression of ISG15 has been observed in several cancers and hence it has been proposed as a strong candidate cancer diagnostic biomarker. Given the emerging relationship between malignant transformation and ISG15, we sought to examine the expression pattern of this gene in tumor biopsies of oral squamous cell carcinoma (OSCC) tissues collected from Indian patients. Total RNA isolated from thirty oral squamous cell carcinoma tissue biopsy samples were subjected to semi-quantitative RT-PCR with ISG15 specific primers to elucidate the expression level. Of the thirty oral squamous cell carcinomas that were analyzed, ISG15 expression was found in twenty four samples (80%). Twelve samples expressed low level of ISG15, six of them expressed moderately, while the rest of them expressed very high level of ISG15. To the best of our knowledge, the results show for the first time an overexpression of ISG15 in up to 80% of oral squamous cell carcinoma tissues collected from Indian patients. Hence ISG15 may be explored for the possibility of use as a high confidence diagnostic biomarker in oral cancers.

Expression of Matrix Metalloproteinase-13 and Ki-67 in Nonmelanoma Skin Cancer in Xeroderma Pigmentosum and Non-xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a heterogenous group of genetic diseases in which basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer (NMSC) followed by squamous cell carcinoma (SCC). The aim of this study was to investigate the expression of matrix metalloproteinase (MMP)-13 and Ki-67 in SCC and BCC from patients with and without XP to elucidate their roles in the pathogenesis of these highly aggressive tumors in patients with XP. Immunolabeling using MMP-13 and Ki-67 antibodies was performed on tissue sections derived from skin biopsies of SCC and BCC of 15 patients with XP and 40 non-XP patients. There was no significant difference between XP and non-XP patients as regards MMP-13 expression by epithelial and stromal cells of SCC or BCC. Ki-67 expression in SCC and BCC of patients with XP was significantly higher than in non-XP patients. We concluded that the higher expression of Ki-67 in NMSC of patients with XP than of non-XP patients may reflect the growth and invasive capacity of these tumors in patients with XP. MMP-13 is expressed by tumor epithelial cells, stromal and inflammatory cells of NMSC of both XP and non-XP patients.

Use of double-bladed biopsy in distinguishing keratoacanthoma from squamous cell carcinoma-a case report

“The SCC Biopsy Tool” (name provided by current authors) is a double-bladed scalpel handle (manufactured and distributed by Surgidental Instruments, Deer Park, NY, USA) with two No. 11 scalpel blades (Swann-Morton, Sheffield, England) set in parallel, 1.5 mm apart (Figure 1). It provides an alternative to other partial biopsy methods and provides advantages over established techniques of shave and punch biopsy, particularly in differentiating squamous cell carcinoma (SCC) from keratoacanthoma (KA) on the leg and foot. The method of obtaining a full-thickness sample across the total width of a lesion with histologic sectioning in a longitudinal plane enables both architecture and cytology to be assessed accurately; precisely the requirement for distinguishing SCC from KA. The advantage over traditional incisional biopsy with a single blade is precision of parallel edges in a situation where central keratin provides an obstacle to such precision.

Podoplanin and E-cadherin Expression in Preoperative Incisional Biopsies of Oral Squamous Cell Carcinoma Is Related to Lymph Node Metastases

Metastases to cervical lymph nodes (LNs) are an important independent adverse indicator in the prognosis of oral squamous cell carcinoma (OSCC). An accurate evaluation of molecular patterns favoring the metastatic process can be helpful in predicting cases of OSCC with elevated probability of early or late metastases and, moreover, in planning the proper therapeutic procedures before surgery. To this end, immunohistochemical expressions of both E-cadherin and podoplanin were evaluated on preoperative incisional biopsies of OSCC from 102 patients. The probability to have or develop metastases was very low when high E-cadherin expression was found in a preoperative sample or when a low podoplanin expression was found. Therefore, because of the strong association with LN metastases, high E-cadherin/low podoplanin immunohistochemical expression should also be assessed on preoperative incisional biopsies as a useful tool for evaluating the probability of early or late LN metastases of OSCCs.

T-box transcription factor Brachyury expression is correlated with epithelial-mesenchymal transition and lymph node metastasis in oral squamous cell carcinoma

The prognosis of patients with oral squamous cell carcinoma (SCC) is influenced by the presence of lymph node metastasis. Epithelial-mesenchymal transition (EMT), a process that involves events that convert adherent epithelial cells into individual migratory cells that can invade the extracellular matrix, is critical for cancer progression. Recently, the T-box transcription factor Brachyury was reported to promote EMT in human carcinoma cell lines. We analyzed the relationship between EMT (assessed by staining for E-cadherin and Vimentin) and the expression of Brachyury in association with lymph node metastasis in oral SCC. Oral SCC biopsy specimens (152 cases) were examined immunohistochemically for the expression of E-cadherin, Vimentin and Brachyury. Expression of Brachyury was correlated with EMT (p=0.035) and was significantly associated with lymph node and distant metastasis (p<0.05). Logistic regression analysis showed that Brachyury and EMT were predictive factors for lymph node metastasis (odds ratio 4.390 and 5.936, respectively) and that EMT was a predictive factor for distant metastases (odds ratio 11.786). Our findings present clinical evidence for an important role of Brachyury in EMT in oral SCC, and suggest that Brachyury and EMT patterns are useful prognostic markers.

Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies

HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies including Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies.

Evaluation of Langerhans cells counts comparing HIV-positive and negative anal squamous cell-carcinoma patients

To investigate the differences in Langerhans cells (LCs) populations between HIV-positive and negative anal squamous cell carcinomas patients. Twenty five patients (14 HIV-positive and 11 HIV-negative) were evaluated. Paraffin-block transversal thin sections from biopsies of anal squamous cell carcinomas (ASCC) were stained using the anti-CD1A antibody that identifies activated LCs. LCs counts were performed using histometry at 20 different sites, at baseline in the ASCC cases. These were then compared with LCs counts in anal canal specimens from HIV-negative and positive patients without ASCC (controls groups). In patients with ASCC, the LC count was greater among HIV-negative individuals than among HIV-positive individuals (p<0.05). The LC count was greater in the control HIV-negative group than in HIV-positive patients with ASCC (p<0.05). There was a lower amount of activated LCs in HIV-positive patients with anal squamous cell carcinomas than in HIV-negative patients, thereby suggesting worsening of the immune response.

Effects of Preoperative Biopsies on Recurrence in Head and Neck Skin Cancer

BackgroundSkin cancer is the most common malignant tumor in humans. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most common types of skin cancers. When skin cancer is clinically suspected, preoperative biopsies are recommended for a definite diagnosis. However, despite a concern over potential increased risk of metastasis associated with mechanical manipulation, there have been few investigations into whether a preoperative biopsy affected the recurrence of BCC and SCC.MethodsPrimary BCC or SCC patients who underwent standard surgical excision from 1991 to 2010 were reviewed and a retrospective analysis was performed. Ultimately, 45 BCC patients and 54 SCC patients, who did not meet the exclusion criteria, were analyzed. To identify whether a preoperative biopsy affected the recurrence of BCC and SCC, the recurrence rates of each with and without biopsy were compared.ResultsPreoperative biopsy had no statistically significant effect on recurrence (BCC, P=0.8680; SCC, P=0.7520). Also, there was no statistical significance between the interval from initial biopsy to first operation and recurrence (BCC, P=0.2329; SCC, P=0.7140). Even though there was no statistical significance, the mean interval from the biopsy to the operation among the BCC patients who underwent preoperative biopsy was 9.2 months in those who had recurrence and 2.0 months in those who had no recurrence.ConclusionsThere was no statistically significant relationship between preoperative biopsy and recurrence of BCC and SCC. However, there was a tendency toward recurrence in patients with a longer interval between the biopsy and the corrective operation in BCC.

Histology differentiation in non-small cell lung cancer using matrix-assisted laser desorption/ionization mass spectrometry.

e21043 Background: New developments in the treatment of lung cancer have necessitated the correct histologic differentiation between two major histologic types of NSCLC. Methods: Histology-directed tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of common solid tumors. In this approach, mass spectra are obtained from discrete locations on the thin sections of frozen tissues sections. In this study, we evaluated various MALDI MS protocols for the histopathologic classification of NSCLC. Results: When adenocarcinoma and squamous cell carcinoma biopsy samples were compared for protein profile using standard sinapinic acid matrix, the median prediction accuracy of the best histology classifier in test sets was 83.3% in 100 random training-to-test partitions (feature selection P &lt;0.05). When 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid matrices were used for lipid MALDI MS, the median prediction accuracy of the best histology classifier in test sets was 85.7% in 100 random partitions (feature selection P&lt;0.01). We then validated the discriminatory lipid profile using independent set of 51 NSCLC surgical samples. Eleven discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set. Phosphatidylcholine 32:0 (m/z 756.68) was overexpressed in adenocarcinomas. Conclusions: Due to the small amount of tissue required for MALDI analysis, rapid experimental procedure, and high predictive values documented in this study, histology-directed MALDI MS, especially lipid profiling, may be a promising approach to the histologic classification of NSCLC (This work was supported by Converging Research Center Program through the Ministry of Education, Science and Technology of Korea (2010K001121)).

Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma

Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion, and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), an aggressive tumor with poor prognosis, as compared with normal tissue. The main IdoA-producing enzyme, DS epimerase 1 (DS-epi1), together with the 6-O- and 4-O-sulfotransferases, were highly upregulated in ESCC biopsies. Importantly, CS/DS structure in patient tumors was significantly altered compared with normal tissue, as determined by sensitive mass spectrometry. To further understand the roles of IdoA in tumor development, DS-epi1 expression, and consequently IdoA content, was downregulated in ESCC cells. IdoA-deficient cells exhibited decreased migration and invasion capabilities in vitro, which was associated with reduced cellular binding of hepatocyte growth factor, inhibition of pERK-1/2 signaling, and deregulated actin cytoskeleton dynamics and focal adhesion formation. Our findings show that IdoA in DS influences tumorigenesis by affecting cancer cell behavior. Therefore, downregulation of IdoA by DS-epi1 inhibitors may represent a new anticancer therapy.

Adenomatous Eccrine Metaplasia—A Novel Reaction Pattern

We recently observed atypical adenomatous metaplasia of eccrine glands in an excisional biopsy of squamous cell carcinoma (SCC). This led us to this study in an effort to ascertain whether this reaction pattern is common to all excisional biopsies and, depending on its presence in association with residual tumor, whether it is lineage specific. We performed a retrospective review of 201 excisional biopsies and noted that adenomatous metaplasia was present in 35 of 201 (17%) of the cases, of which 19 had residual tumor. Adenomatous metaplasia seemed to be more frequent in epithelial neoplasms such as basal cell carcinomas 15 of 94 (16%) and SCCs 13 of 61 (21%) although only (3 of 41) 7% of nevomelanocytic proliferations exhibited this change. Residual tumor was noted in association with adenomatous metaplasia, in 11 of 15 cases (73%) in the basal cell carcinoma subgroup, in 8 of 13 cases (62%) in the SCC subgroup, and in none from the nevomelanocytic subgroup. Comparing frequencies of adenomatous metaplasia across groups, only SCC specimens with residual tumor demonstrated a statistically significant increase compared with nevomelanocytic neoplasm (35% vs. 7%, P = 0.01). Findings from the current study expand the spectrum of metaplastic change involving eccrine glands to include adenomatous metaplasia. Given that it seems to be more common to epithelial malignancies, it seems reasonable to posit that this reaction pattern is the consequence of hitherto undefined proteins induced by epithelial tumor cells resulting in exuberant stimulation of eccrine glands, although immunohistochemical and molecular studies are required to define the precise cause.

Risk Estimation for a Malignant Transformation of Oral Lesions by S100A7 and Doc-1 Gene Expression

The objective of this study was the correlation of Doc-1- and S100A7-gene expression in common oral lesions with their cancerous-transformation risk. Biopsies (n = 15 each) of healthy gingiva, irritation fibromas, leukoplakias and Oral squamous cell carcinoma (OSCCs) were obtained, and after RNA-extraction, transcripts of Doc-1 and S100A7 were quantified by RT-PCR. In comparison with the healthy gingiva, the expression of Doc-1 was decreased, whereas the expression of S100A7 was upregulated in all lesions. As the extent of Doc-1-inactivation and S100A7-overexpression is correlated with their biological behavior, the combined investigation of both genes could be a promising marker in intraoral lesions to estimate the risk for their malignant transformation.