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Paraffin-embedded Specimens (paraffin-embedded + specimen)
Selected AbstractsDetection of human papillomavirus DNA in squamous cell carcinoma of the esophagus by auto-nested PCRDISEASES OF THE ESOPHAGUS, Issue 2 2006A. P. Souto Damin SUMMARY., The aim of the present study was to investigate the presence of human papillomavirus (HPV) in surgical specimens of esophageal squamous cell carcinoma. One hundred and sixty-five paraffin-embedded specimens of esophageal carcinoma were analyzed through high-sensitivity auto-nested polymerase chain reaction (PCR) using the consensus GP5+/GP6+ primer. Twenty-six specimens of esophageal mucosa without malignant disease were also studied as a control group. Two different specific primer sets targeting the E6 region of the HPVs 16 and 18 were used for typing. Direct DNA sequence analysis was conducted to confirm positive PCR results. HPV DNA was detected in 26 esophageal carcinomas (15.75%), but in none of the benign esophageal specimens (P < 0.05). Out of the 26 positive cases, 24 were HPV-16 and one was HPV-18. One tumor contained both HPV-16 and -18 DNA. Positive PCR results were confirmed by the amplified viral sequences. Our findings suggest that the presence of either HPV-16 or -18 might be related to development of the malignant phenotype in the esophagus. [source] Functional estrogen receptors alpha and beta are expressed in normal human salivary gland epithelium and apparently mediate immunomodulatory effectsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2009Maria Tsinti Salivary gland epithelial cells (SGECs) have been shown to participate in immunological responses and have been implicated in the pathogenesis of Sjögren's syndrome (SS). Experimental evidence from animal models indicates that estrogen deficiency may also participate in SS pathogenesis. However, the expression and functionality of the estrogen receptors alpha (ER,) and beta (ER,) in normal human salivary epithelium is unknown. To investigate these points, formalin-fixed, paraffin-embedded specimens and cultured non-neoplastic SGEC lines derived from nine minor salivary gland (MSG) biopsies with normal histology were studied. Immunohistochemical analyses detected the epithelial expression of ER,, ER,1, and ER,2 protein isoforms both in MSG tissues and in cultured SGECs. Such epithelial expression was verified by immunoblotting of various ER proteins in cellular extracts of cultured SGECs (full-length-ER,, ER,-,3, ER,1-long, ER,1-short, and ER,2-long isoforms). Estrogens did not induce growth or apoptosis in cultured SGECs. However, similarly to other cellular systems, treatment of cultured SGECs with estrogens (17,-estradiol and the ER,- and ER,-selective agonists propylpyrazole-triol and diarylpropiolnitrile, respectively) inhibited the interferon-,-inducible expression of intercellular adhesion molecule-1. This finding corroborated the functionality of ER expressed by SGEC. Our results suggest that salivary epithelium expresses constitutively functional ER, and ER, proteins that apparently mediate immunomodulatory effects. [source] Immunohistochemical study of epidermal growth factor receptor in adenoid cystic carcinoma of salivary gland originHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2002Marilena Vered DMD Abstract Background Epidermal growth factor (EGF) and its receptor (EGFR) are involved in the development of salivary gland tumors. Recently, treatment modalities for EGFR inhibition have shown an enhanced clinical response in carcinomas of different locations. Adenoid cystic carcinoma (ACC) of salivary gland origin is a malignant tumor with a poor long-term outcome. If salivary gland ACC does exhibit EGFR, then immunotherapy could have a major impact on improving its prognosis. Methods The study consisted of 34 samples of formalin-fixed, paraffin-embedded specimens of salivary gland ACC. Specimens were stained with a mouse antihuman monoclonal antibody for immunohistochemical detection of EGFR. Overlying oral mucosa and adjacent normal salivary ducts served as internal controls. Both membrane and cytoplasmic staining were evaluated. Staining score was calculated by multiplying the percentage of positively stained tumor cells by the intensity of the staining. The highest score for a given tumor was equal to 2. Results In the final analysis, 27 of the 34 specimens were included; 7 were excluded, because the internal control did not reveal any staining. Of these 27 specimens, 23 (85%) stained positively for EGFR with a staining score of 0.05 to 1.8. Three palatal tumors attained the highest scores (one tumor, 1.2, and the remaining two, 1.8). Conclusions Most salivary gland ACC stained positively for EGFR, and in some the staining was quite intense. On the basis of the already proven antitumoral effect of agents acting as EGFR inhibitors, it is suggested that patients with ACC might benefit from these agents, especially when surgery has failed or in those with recurrent or metastatic disease. © 2002 Wiley Periodicals, Inc. Head Neck 24: 632,636, 2002 [source] Thymidylate synthase and dihydropyrimidine dehydrogenase gene expression in relation to differentiation of gastric cancerINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Wataru Ichikawa Abstract Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes of DNA de novo synthesis and the salvage pathway in cancer cells, respectively. Intratumoral TS and DPD gene expressions were evaluated to determine the correlation between the expression of the 2 genes in both normal stromal tissues and tissues with different degrees of malignant differentiation in primary gastric cancer. The study population consisted of 78 consecutive patients with advanced gastric cancer who underwent surgical treatment. Laser-captured microdissection of malignant or normal stromal tissues was performed in formalin-fixed, paraffin-embedded specimens. After extraction of RNA, TS and DPD gene expressions were measured by the real-time reverse transcriptional PCR method. Apart from degree of differentiation, TS and DPD in malignant tissue showed no correlation with clinicopathologic factors. TS in malignant tissue was higher in differentiated type cases than undifferentiated type cases (p < 0.01). However, DPD in malignant tissue of undifferentiated type cases was statistically higher than that of differentiated type cases (p < 0.05). In normal stromal tissue, neither TS nor DPD had any correlation with clinicopathologic factors. TS in malignant tissue was statistically higher than in normal stromal tissue in both differentiated and undifferentiated types (p < 0.0001). DPD in differentiated type malignant tissue was statistically lower than in normal stromal tissue (p < 0.001), but no difference was seen in undifferentiated type cases. TS and DPD gene expressions in primary gastric cancer differ according to degree of differentiation and between malignant and normal stromal tissue. © 2004 Wiley-Liss, Inc. [source] Reduced expression of CD9 in oral squamous cell carcinoma: CD9 expression inversely related to high prevalence of lymph node metastasisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2001Jingo Kusukawa Abstract: Because CD9 is implicated in cell growth, cell adhesion and cell motility, altered CD9 expression might be involved in cancer invasion and metastasis. We have studied the immunolocalization of CD9 in oral squamous cell carcinoma (SCC). Sections prepared from paraffin-embedded specimens from patients with SCC of the oral cavity were stained with a monoclonal anti-CD9 antibody by means of the streptoavidin biotin method. Significant reduction or complete loss of CD9 expression was observed in cancer cells at the periphery of the cancer nests in the advancing front of invading tumor. Among 78 cases of oral SCCs examined, 46 (59.0%) cases were completely negative for CD9 expression. Loss of CD9 expression in cancer tissue strongly correlated with a high incidence of cervical lymph node metastasis and poorer prognosis (P=0.001). Thus a close examination of CD9 in SCC tissue would be useful for the prognosis of patients with oral carcinoma. [source] CNS lymphomatoid granulomatosis with lymph node and bone marrow involvementsNEUROPATHOLOGY, Issue 6 2008Akihiro Takiyama Lymphomatoid granulomatosis (LYG) in the CNS is an uncommon lymphoproliferative disease with characteristic angiocentric lymphoreticular proliferative and granulomatous lesions exhibiting low-grade malignant potential. Here we report a rare case of CNS-LYG, which disseminated to the lymph node and bone marrow. A 50-year-old man was diagnosed with CNS-LYG based on brain biopsy showing perivascular infiltration of CD3-positive small T-lymphocytes without overt nuclear atypism. Eight months after the initial neurological symptoms, inguinal lymph node swelling was found and histopathologically diagnosed as peripheral T-cell lymphoma. TCR,-gene rearrangement study using both paraffin-embedded specimens of brain and inguinal lymph node demonstrated an identical clonal band. Considering the clinical course, we concluded lymph node involvement of CNS-LYG, suggesting the malignant potential of CNS-LYG. [source] Mutations of the BRAF gene in papillary thyroid carcinoma and in Hashimoto's thyroiditisPATHOLOGY INTERNATIONAL, Issue 9 2005Kyung-Hee Kim The purpose of the present study was to investigate the frequency of BRAF mutations in human papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) and to evaluate the association of the BRAF mutation with the clinicopathological features of both of these thyroid disorders. A total of 51 PTC with no HT, 28 PTC with HT and 27 HT with no PTC were evaluated using DNA extracted from paraffin-embedded specimens. BRAF mutations were analyzed by direct DNA sequencing of the polymerase chain reaction (PCR)-amplified exon 15. The BRAF missense mutation at codon 599 (T1796A) was present in 46 of 51 PTC (90%) with no HT, 18 of 28 PTC (64%) with HT, four of 28 HT (14%) with PTC, and zero of 27 HT with no PTC. The BRAF mutation at codon 600 (A1798G) was not detected in any case. Clinicopathological examination of 106 patients with either PTC or HT showed that the BRAF mutation was significantly correlated with patient age. These data indicate that the BRAF mutation is associated with a valuable biological property of PTC and may participate in the pathogenesis of PTC arising in HT. These results indicate that the detection of the BRAF mutation in HT can be helpful for prediction of progress to PTC. [source] OCT4: biological functions and clinical applications as a marker of germ cell neoplasiaTHE JOURNAL OF PATHOLOGY, Issue 1 2007L Cheng Abstract Germ cell tumours (GCTs) are a heterogeneous group of neoplasms, which develop in the gonads as well as in extragonadal sites, that share morphological patterns and an overall good prognosis, owing to their responsiveness to current surgical, chemotherapeutic, and radiotherapeutic measures. GCTs demonstrate extremely interesting biological features because of their close relationships with normal embryonal development as demonstrated by the pluripotentiality of some undifferentiated GCT variants. The similarities between GCTs and normal germ cell development have made it possible to identify possible pathogenetic pathways in neoplastic transformation and progression of GCTs. Genotypic and immunophenotypic profiles of these tumours are also useful in establishing and narrowing the differential diagnosis in cases of suspected GCTs. Recently, OCT4 (also known as OCT3 or POU5F1), a transcription factor that has been recognized as fundamental in the maintenance of pluripotency in embryonic stem cells and primordial germ cells, has been proposed as a useful marker for GCTs that exhibit features of pluripotentiality, specifically seminoma/dysgerminoma/germinoma and embryonal carcinoma. The development of commercially available OCT4-specific antibodies suitable for immunohistochemistry on paraffin-embedded specimens has generated increasing numbers of reports of OCT4 expression in a wide variety of gonadal and extragonadal GCTs. OCT4 immunostaining has been shown to be a sensitive and specific marker for seminomatous/(dys)germinomatous tumours and in embryonal carcinoma variants of non-seminomatous GCTs, whether in primary gonadal or extragonadal sites or in metastatic lesions. Therefore, OCT4 immunohistochemistry is an additional helpful marker both in the differential diagnosis of specific histological subtypes of GCTs and in establishing a germ cell origin for some metastatic tumours of uncertain primary. OCT4 expression has also been reported in pre-invasive conditions such as intratubular germ cell neoplasia, unclassified (IGCNU) and the germ cell component of gonadoblastoma. Additionally, OCT4 immunostaining shows promise as a useful tool in managing patients known to be at high risk for the development of invasive GCTs. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer,THE LARYNGOSCOPE, Issue 7 2005Larry E. Morrison PhD Objectives/Hypothesis: Epidermal growth factor receptor (EGFR) over-expression has been reported as a prognostic indicator in laryngeal cancer; however, the association with disease outcome has been inconsistent among studies. Here, we use fluorescence in situ hybridization (FISH) in addition to immunohistochemistry to assess laryngeal squamous cell carcinoma (SCC) to determine whether FISH can better predict patient outcome. Study Design: Retrospective study on 59 patients presenting with advanced disease. Methods:EGFR and chromosome 7 genomic statuses were measured using FISH, and EGFR expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded specimens and correlated with outcome in the 59 patients. Results: EGFR expression was marginally associated with outcome, whereas both EGFR and chromosome 7 FISH status were significantly associated with outcome, and the combination of EGFR and chromosome 7 FISH status provided the strongest association of any two combined parameters (P = .0004). Combining EGFR expression with EGFR and chromosome 7 FISH status provided further improvement (P > .0001). Conclusions: Measurements of EGFR and chromosome 7 FISH status, and to a lesser extent EGFR expression, have potential value in treatment planning for patients with laryngeal SCC. [source] Neural Cell Adhesion Molecule Expression in Adenoid Cystic Carcinoma of the Head and Neck,THE LARYNGOSCOPE, Issue 6 2000James A. Hutcheson MD Abstract Objective To investigate whether there is a correlation between neural cell adhesion molecule (NCAM) expression and perineural spread in patients with adenoid cystic carcinoma of the head and neck (ACCHN). Study Design Retrospective review of medical records and immunohistochemical staining of specimens from 37 patients treated at the University of Arkansas in Little Rock from 1987 to 1997. Methods Sections from paraffin-embedded specimens were e-amined for the presence of NCAM using monoclonal anti-NCAM antibody by avidin-biotin-pero-idase immunohistochemical staining. NCAM staining was scored in each specimen and correlated with the data obtained from patient charts. Results Twenty-five of 37 specimens (68%) showed histopathological evidence of perineural spread. All 37 specimens (100%) stained positive for NCAM, regardless of perineural spread status. Conclusion Our results suggested that the use of NCAM expression as a predictor of perineural spread is highly unlikely. [source] Heparin-binding epidermal growth factor-like growth factor isoforms and epidermal growth factor receptor/ErbB1 expression in bladder cancer and their relation to clinical outcomeCANCER, Issue 10 2007Christopher Kramer MD Abstract BACKGROUND. Cleavage of membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields a soluble HB-EGF isoform (sHB-EGF), which is an activating epidermal growth factor receptor (EGFR) ligand and a C-terminal fragment HB-EGF-C acting directly in the nucleus. In bladder cancer, overexpression of both HB-EGF and EGFR have been observed, but to the authors' knowledge the prognostic significance of different modes of HB-EGF signaling have remained unclear. METHODS. Expression and intracellular localization of HB-EGF and EGFR were examined by immunohistochemistry in paraffin-embedded specimens from 121 patients who underwent cystectomy for bladder cancer. Tumor stage was pTis/pT1 in 7 patients, pT2 in 41 patients, pT3 in 55 patients, and pT4 in 18 patients. Lymph node metastases were present in 32 patients. RESULTS. Using an antibody directed against the C-terminal domain, HB-EGF expression was detected in the cytoplasm or in the nucleus of tumor cells. EGFR staining was uniform at the plasma membrane. The actuarial 5-year cancer-specific survival of patients with tumors with predominant nuclear HB-EGF staining was 28% compared with 57% if HB-EGF staining was predominantly cytoplasmic (P = .027). Disease outcome of patients with a ,mixed' HB-EGF staining pattern was found to be between that of the 2 former groups. In agreement with previous studies, strong EGFR expression was associated with poor prognosis. Despite strong EGFR expression, predominant cytoplasmic HB-EGF staining was associated with a more favorable outcome, whereas a predominant nuclear pattern defined a subgroup with extremely poor prognosis (5-year tumor-specific survival of 55% vs 13%, respectively; P = .026). CONCLUSIONS. The current study results confirm that EGFR expression is significantly correlated with disease-specific mortality but that the outcome is also influenced by the mode of HB-EGF signaling. Additional nuclear HB-EGF signaling, indicative of increased cleavage of proHB-EGF, appears to enhance the adverse activities. Cytoplasmic HB-EGF staining likely reflects proHB-EGF, which may also exert antiproliferative effects. Cancer 2007. © 2007 American Cancer Society. [source] Mononuclear cell infiltration in clear-cell renal cell carcinoma independently predicts patient survivalCANCER, Issue 1 2006W. Scott Webster MD Abstract BACKGROUND The impact of mononuclear cell infiltration on renal cell carcinoma (RCC) biology has been controversial, previously reported to be associated with either a favorable or unfavorable prognosis. The objective of the current study was to evaluate associations between mononuclear cell infiltration in routinely prepared paraffin-embedded specimens with survival in patients with clear-cell RCC. METHODS A total of 306 patients were identified treated with nephrectomy for clear-cell RCC between 1990 and 1994. A single urologic pathologist, blinded to patient outcome, reviewed the specimens and quantified the extent of mononuclear cell infiltration as absent, focal, moderate, or marked. Cancer-specific survival was estimated using the Kaplan,Meier method. Associations of mononuclear cell infiltration with death from RCC were assessed using Cox proportional hazards regression models. RESULTS At last follow-up, 173 of the 306 patients studied had died, including 96 patients who died from RCC. Mononuclear cell infiltration was absent in 165 (54%), focal in 70 (23%), moderate in 53 (17%), and marked in 18 (6%). Univariately, patients with specimens that had mononuclear cell infiltration were over 2 times more likely to die from RCC compared with patients whose specimens exhibited no mononuclear cell infiltration (risk ratio, 2.63; P<.001). After adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score, patients with specimens that had mononuclear cell infiltration exhibited a significantly increased likelihood of dying from RCC compared with patients whose specimens had no mononuclear cell infiltration (risk ratio, 1.61; P = .028). CONCLUSIONS Mononuclear cell infiltration is associated with death from RCC even after multivariate adjustment. Routine documentation of mononuclear cell infiltration is recommended during the pathologic assessment of RCC. Cancer 2006. © 2006 American Cancer Society. [source] The analysis of immunophenotype of gastrin-producing tumors of the pancreas and gastrointestinal tractCANCER, Issue 9 2003Larissa Gurevich M.D., Ph.D. Abstract BACKGROUND Gastrinomas are located more frequently in the pancreas, which normally has no cells that can produce gastrin. They have a more aggressive course than other pancreatic endocrine tumors and extrapancreatic gastrinomas associated with multiple endocrine neoplasia Type 1 syndrome. The current study analyzed immunophenotypes of gastrinomas and compared them with other pancreatic endocrine tumors. METHODS Twenty-one formalin-fixed, paraffin-embedded specimens (15-tumors in the pancreas, 1 in the duodenum, 1 in the stomach, 1 in the liver, and 3 of unknown primary location) accompanied by Zollinger,Ellison syndrome and 17 other pancreatic endocrine tumor specimens were investigated. They were stained immunohistochemically for gastrin, chromogranin A, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, calcitonin, serotonin, chorionic gonadotropin, adrenocorticotropic hormone, carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin 19. RESULTS Gastrinomas coexpressed neuroendocrine and exocrine markers, including chromogranin A, synaptophysin, carcinoembryonic antigen, cytokeratin 19, and epithelial membrane antigen. Carcinoembryonic antigen was found in all 17 gastrinomas (100%), cytokeratin 19 was found in 15 of 17 (88.2%) gastrinomas, and epithelial membrane antigen was found in 16 of 18 (88.9 %) gastrinomas. Cytokeratin 19, epithelial membrane antigen, and carcinoembryonic antigen were not found to be present in the pancreatic endocrine tumors, but chromogranin A and synaptophysin were. Chorionic gonadotropin was found in 16 gastrinomas (100%), but only in 2 of 17 other pancreatic endocrine tumors (11.8 %). CONCLUSIONS Pancreatic gastrinomas were characterized by the coexpression of neuroendocrine markers, exocrine markers, and chorionic gonadotropin. Therefore, pancreatic gastrinomas made a special intermediate group of tumors, which phenotypically combined features of neuroendocrine and exocrine neoplasms. These findings suggested that sporadic pancreatic gastrinomas and other pancreatic endocrine tumors are different phenotypically and are possibly of different origin. Cancer 2003. © 2003 American Cancer Society. [source] | ||||||||||||||||||||||