Supraglottic and glottic carcinomas: Epidemiologically distinct entities?

In the time period 1988-2000, a case-control study on laryngeal cancer was conducted in Montevideo, Uruguay. Four-hundred eighty-one (481) cases newly diagnosed and microscopically confirmed as squamous cell carcinomas were included. These cases were frequency matched with 481 nonneoplastic controls, admitted to the same hospitals as the cases. The purpose of our study was to compare odds ratios (ORs) by laryngeal subsite (supraglottis and glottis). ORs of supraglottic cancers displayed much higher risks than glottic carcinomas for most tobacco variables and for red wine intake. The differences between subsites were statistically significant, displaying heterogeneity between both subsites. Moreover, whereas black tobacco smokers displayed a significant increased risk of 1.7 (95% confidence interval [CI] 1.2-2.5) compared to smokers of blond (flue-cured) tobacco among supraglottic tumors, no effect of this type of tobacco was observed in glottic lesions. It could be suggested that concerning tobacco and alcohol effects, supraglottic and glottic squamous cell cancers are probably distinct epidemiologic entities.     

Cancer stem cells: distinct entities or dynamically regulated phenotypes?

The origins of tumor-propagating neoplastic stem-like cells [cancer stem cells (CSC)] and their relationship to the bulk population of tumor cells that lack stem-like tumor-propagating features (i.e., transit-amplifying cancer progenitor cells) remain unclear. Recent findings from multiple laboratories show that cancer progenitor cells have the capacity to dedifferentiate and acquire a stem-like phenotype in response to either genetic manipulation or environmental cues. These findings suggest that CSCs and relatively differentiated progenitors coexist in dynamic equilibrium and are subject to bidirectional conversion. In this review, we discuss emerging concepts regarding the stem-like phenotype, its acquisition by cancer progenitor cells, and the molecular mechanisms involved. Understanding the dynamic equilibrium between CSCs and cancer progenitor cells is critical for the development of therapeutic strategies to deplete tumors of their tumor-propagating and treatment-resistant cell subpopulations.     

Familial colorectal cancer type X syndrome: two distinct molecular entities?

In a fraction of families fulfilling the Amsterdam criteria for hereditary non-polyposis colorectal cancer, colorectal cancers are microsatellite stable and DNA mismatch repair gene (MMR) mutations are not found. These families were designated as familial colorectal cancer type X (FCCTX). We aimed to characterise a group of FCCTX families defined by the Amsterdam criteria and MSS tumours at clinical and molecular level. Twenty-four tumours from 15 FCCTX families were analysed for loss of known tumour suppressor gene (TSG) loci (APC, TP53, SMAD4 and DCC), MGMT and MMR genes promoter methylation, and also APC and KRAS somatic mutations. FCCTX families presented specific clinical features: absence of endometrial tumours, high adenoma/carcinoma ratio (1.91) and prevalence of rectal cancers (13/27, 48%). New molecular features were found: the majority of FCCTX tumours (13/18; 72%) presented TSG loss. TSG loss positive tumours presented frequent APC and KRAS somatic mutations and MGMT methylation [10/13 (77%), 7/13 (54%) and 6/11 (54%), respectively]. In TSG loss negative tumours (5/18; 28%), the same molecular events were found in 2/5 (40%), 2/5 (40%) and 1/3 (33%) tumours, respectively. Transition mutations in KRAS were more frequent among MGMT methylated tumours than in unmethylated [5/8 (63%) vs. 1/10 (10%), P?=?0.03]. Although sharing similar clinical features, at least two different molecular entities should exist among FCCTX families, one whose tumours present frequent TSG loss, APC and KRAS somatic mutations, and MGMT promoter methylation, and a second, lesser predominant, with no evidence of TSG loss and rarely presenting promoter methylation.     

Nodal staging of colorectal carcinomas from quantitative and qualitative aspects. Can lymphatic mapping help staging?

Retrospective data analysis was performed to determine the minimum number of lymph nodes required for the staging of colorectal carcinomas, and a prospective feasibility study was carried out to identify sentinel nodes in order to clarify whether these may predict the nodal status. From among 240 colorectal carcinoma specimens investigated between 1996 and 1998, 224 tumors were analyzed for their nodal status. Lymphatic mapping with vital patent blue dye injection into the peritumoral sub-serosal layer was performed in 25 patients. Blue nodes were identified by the pathologist in the unfixed specimen immediately after the resection of the bowel and were assessed separately. Of the 123 node-positive carcinomas, 40 had more than 3 nodes involved. The nodal positivity increased substantially when more than 6 nodes were assessed. The cumulative percentage analysis demonstrated that ideally 16 and 13 nodes should be obtained for the identification of any nodal involvement or the involvement of more than 3 nodes, respectively. Lymphatic mapping was successful in 24 patients (96%). Blue nodes were predictive of the nodal status in 19 cases (79%), and were the only sites of metastasis in 2 patients (15% of the node-positive cases). Lymphatic mapping with the vital blue dye technique does not seem to facilitate the staging of colorectal cancers, at least in our patient population with relatively large and deeply infiltrating tumors, and unless the technique is improved or other selective features of lymph nodes are found, all lymph nodes should be assessed. A minimum of 6 nodes, and an optimum of 16 nodes or more, are suggested from these series.     

Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer?

Prostate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. It emerges through the acquisition of genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications and microRNA deregulation. These generate heritable transformations in the expression of genes but do not change the DNA sequence. Alterations in DNA methylation (hypo and hypermethylation) are the most characterized in PCa. They lead to genomic instability and inadequate gene expression. Major and minor-specific modifications in chromatin recasting are involved in PCa, with signs suggesting a dysfunction of enzymes modified by histones. MicroRNA deregulation also contributes to the initiation of PCa, including involvement in androgen receptor signalization and apoptosis. The influence of inflammation on prostate tumor carcinogenesis is currently much better known. Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation, promoting prostate inflammatory atrophy and eventually leading to PCa. Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa. The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis, treatment decisions, evaluation of prognosis and posttreatment surveillance.     

The role of re-irradiation of secondary and recurrent head and neck carcinomas. Is it a potentially curative treatment? A practical approach

Despite aggressive efforts to cure head and neck cancer patients, including altered fractionation and the addition of chemotherapy to radiation, locoregional recurrence remains a serious issue to face in clinical practice. Indeed, recurrent and second primary tumors occurring in previously irradiated area are common clinical challenge. Whenever possible, patients are advised to undergo salvage surgery. Nevertheless, few patients are suitable candidates for curative resection. In such cases, chemotherapy alone has traditionally been considered, with a poor response rate.     

Uterine serous and grade 3 endometrioid carcinomas: is there a survival difference?

BACKGROUND: Serous components within endometrial carcinoma are reportedly poor prognosticators. However, to the authors' knowledge the percentage of tumors which must be comprised of a serous component in order to affect outcome is unknown. The authors compared overall survival (OS) in women with endometrial carcinomas comprised of various percentages of uterine serous carcinoma (USC) with that of women with International Federation of Gynecology and Obstetrics (FIGO) Grade 3 endometrioid carcinoma (G3EC) to determine whether outcomes varied between these two poorly differentiated histologies. METHODS: Data concerning women with either G3EC or USC who were diagnosed between January 1990 and November 2000 were collected retrospectively. Cases were reviewed to confirm diagnosis and estimate the fraction of tumor comprised of USC. Variables assessed included patient age and race, tumor stage, and lymphovascular space invasion. Associations between variables were tested using the Fisher exact test. The Kaplan-Meier method was used to evaluate OS with comparisons performed using the log-rank test. RESULTS: Fifty-two women with G3EC and 87 women with USC were identified. The OS of women with tumors comprised of > 50% USC was found to be significantly worse compared with women with G3EC (hazard ratio [HR] of 2.4; 95% confidence interval [95% CI], 1.2-5.2). Women with USC were more likely to present with extrauterine disease (odds ratio of 2.2; 95% CI, 1.1-4.5). The 5-year survival rate for women with G3EC was 75% compared with 41% for women with tumors that were > 50% USC (P = 0.01). There was a significant trend toward a worse OS in women with even 10% USC compared with women with G3EC. CONCLUSIONS: USC involving > 50% of an endometrial carcinoma was found to be predictive of worse OS compared with the OS of women with G3EC. In patients with early-stage disease, a trend toward a worse prognosis was found to exist when USC comprised even 10% of a tumor. Investigation into the treatment of endometrial carcinoma should include and document tumors with any percentage comprised of USC.     

Interleukin 8 and vascular endothelial growth factor -- prognostic factors in human gastric carcinomas?

Gastric carcinoma cells express potent angiogenic factors including vascular endothelial growth factor (VEGF). We previously reported that interleukin-8 (IL-8) acts as an angiogenic factor for human gastric carcinomas. More recently, we found that IL-8 upregulates matrix metalloproteinase-9 (MMP-9) expression and increases invasive activity of gastric carcinoma cells. The purpose of this study was to determine whether the expression of IL-8 and VEGF correlates with clinicopathological parameters in human gastric carcinomas. IL-8 and VEGF expression levels were measured by an enzyme-linked immunosorbent assay (ELISA) in 56 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumour findings, presence of metastasis and prognosis were obtained from the patient records and endoscopic, surgical and pathological reports. IL-8 protein levels were higher in most neoplasms than in the corresponding normal mucosal tissue. In contrast, VEGF expression in the tumours was similar to that in normal mucosa. The IL-8 level in the neoplasms correlated significantly with the depth of invasion, venous invasion and lymphatic invasion. VEGF expression in the tumours correlated well with the depth of invasion and lymph node metastasis. No correlation between IL-8 and VEGF expression in the tumours was observed. The survival rates of patients with tumours displaying high IL-8 and VEGF expression levels were significantly lower (P<0.05) than those of patients with tumours displaying low IL-8 and VEGF expression. The results suggest that IL-8 and VEGF may be independent and important prognostic factors in human gastric carcinomas.     

25. Clinicopathologic analysis on 13 823 carcinomas of esophagus and cardia in Chaoshan littoral of China

Background: Chaoshan is the close region and Chaoshan people who came from old Changan and Henan thousands years ago are relative isolation population with high-risk of esophageal carcinoma (EC) and cardiac carcinoma(CC) in China. However there were no report about detail clinicopathologic data of cancer of esophagus and cardia in Chaoshan district before. Methods: The data of age, sex. ABO blood type and X-ray or pathological diagnosis of the patients with carcinoma of esophagus or cardia were collected from The tumor hospital. The First affiliated hospital, The Second affiliated hospital of Shantou University Medical College, the Center hospital of Shantou and the populalion hospital of Jieyang. In this study. Clinicopathologic data of 9 650 patients with EC and 4 173 patients with CC in Chaoshan population were analyzed. Results and Conclusion: The male to female ratio was 3∶1 in EC and 4.75∶1 in CC, indicating EC and CC was more common in the male than in the female. The average affected age of EC was 54.61 year old. CC was 58.14 year old. The most common affected site of esophageal carcinoma was the middle third of esophagus(72.00%); the second was the lower third (15.30%). The main gross type of esophageal carcinoma was ulcerative type (41.50%); the medullary type ranks second (39.60%). In histological types of EC, squamous cell carcinoma accounted for overwhelming majority(96.44%).     

Infantile rhabdomyofibrosarcoma: a distinct variant or a missing link between fibrosarcoma and rhabdomyosarcoma?

Infantile rhabdomyofibrosarcoma (IRMFS) is a rare soft tissue tumour affecting infants and young children. It occupies an intermediate position between infantile fibrosarcoma and spindle cell rhabdomyosarcoma in its clinical presentation, behaviour, morphology, immunohistochemical and ultrastructural features. This case is reported here to reiterate its occurrence as tumour with distinct morphological immunohistochemical and clinical behavioral patterns.