Sadir J. Alrawi

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement

Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer.

BackgroundUncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC).Methods128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis.ResultsOf the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample.ConclusionThe results suggest that higher tumor proliferation and motility may be important in the prognosis of NSCLC, and composite application of biomarkers might be of greater value than single marker application in assessing tumor prognosis.

Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms.

BackgroundThe assessment of tumor invasion of underlying benign stroma in neoplastic squamous proliferation of the larynx may pose a diagnostic challenge, particularly in small biopsy specimens that are frequently tangentially sectioned. We studied whether thresholds of an eosinophilic response to laryngeal squamous neoplasms provides an adjunctive histologic criterion for determining the presence of invasion.MethodsEighty-seven(n = 87) cases of invasive squamous cell carcinoma and preinvasive squamous neoplasia were evaluated. In each case, the number of eosinophils per high power field(eosinophils/hpf), and per 10 hpf in the tissue adjacent to the neoplastic epithelium, were counted and tabulated. For statistical purposes, the elevated eosinophils were defined and categorized as: focally and moderately elevated (5–9 eos/hpf), focally and markedly increased(>10/hpf), diffusely and moderately elevated(5–19 eos/10hpf), and diffusely and markedly increased (>20/10hpf).ResultsIn the invasive carcinoma, eosinophil counts were elevated focally and /or diffusely, more frequently seen than in non-invasive neoplastic lesions. The increased eosinophil counts, specifically >10hpf, and >20/10hpf, were all statistically significantly associated with stromal invasion. Greater than 10 eosinophils/hpf and/or >20 eosinophils/10hpf had highest predictive power, with a sensitivity, specificity and positive predictive value of 82%, 93%, 96% and 80%, 100% and 100%, respectively. Virtually, greater than 20 eosinophils/10 hpf was diagnostic for tumor invasion in our series.ConclusionOur study suggests for the first time that the elevated eosinophil count in squamous neoplasia of the larynx is a morphologic feature associated with tumor invasion. When the number of infiltrating eosinophils exceeds 10/hpf and or >20/10 hpf in a laryngeal biopsy with squamous neoplasia, it represents an indicator for the possibility of tumor invasion. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should prompt a thorough evaluation for invasiveness, when evidence of invasion is absent, or when invasion is suspected by conventional criteria in the initial sections.

Aberrant crypt foci as precursors in colorectal cancer progression.

Colorectal cancer progression originates when accumulated genetic and epigenetic alterations cause genomic instability and a malignant phenotype. Subsequent molecular pathway deregulation leads to histopathologic changes that are clinically evident as aberrant crypt foci (ACF) and visualized by high‐magnification chromoscopic colonoscopy. ACF are biomarkers of increased colorectal cancer risk, particularly those with dysplastic features. Genetic profiling using genomic instability, loss of heterozygosity, and methylation analysis has revealed a minority population of ACF genotypically analogous to cancer. J. Surg. Oncol. 2008;98:207–213.

Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma

BackgroundDistinguishing endocervical adenocarcinoma (ECA) from endometrial mucinous adenocarcinoma (EMMA) is clinically significant in view of the differences in their management and prognosis. In this study, we used a panel of tumor markers to determine their ability to distinguish between primary endocervical adenocarcinoma and primary endometrial mucinous adenocarcinoma.MethodsImmunohistochemistry using monoclonal antibodies to MUC1 (Ma695), p16, estrogen receptor (ER), progesterone receptor (PR), and vimentin, was performed to examine 32 cases, including 18 EMMAs and 14 ECAs. For MUC1, cases were scored based on the percentage of staining pattern, apical, apical and cytoplasmic (A/C), or negative. For p16, cases were scored based on the percentage of cells stained. For the rest of the antibodies, semiquantitative scoring system was carried out.ResultsFor MUC1, majority of EMMA (14 of 18 cases, 78%) showed A/C staining, whereas only few ECA (2 of 14, 14%) were positive. The difference of MUC1 expression in the two groups of malignancy was statistically significant (p < 0.001). Staining for p16 was positive in 10 of 14 (71%) ECA and 4 of 18 (22%) EMMA. Estrogen receptor was positive in 3 of 14 (21%) ECA and 17 of 18 (94%) EMMA. Progesterone receptor was positive in 3 of 14 (21%) ECA and 16 of 18 (89%) EMMA. Vimentin was positive in 1 of 14 (7%) ECA, and 9 of 18 (50%) EMA, with median and range of 0 (0–6), and 1.5 (0–9) respectively.ConclusionA panel of immunohistochemical markers including MUC1, p16, ER, PR, and vimentin is recommended, when there is morphological and clinical doubt as to the primary site of endocervical or endometrial origin.

Lipomatous hemangiopericytoma of the head and neck: immunohistochemical and dna ploidy analyses

Lipomatous hemangiopericytoma (LHPC) is a newly described rare soft tissue tumor with unpredictable biologic behavior and is difficult to diagnose by conventional histologic parameters. The molecular analyses of this entity to date are sparse. Only a few cases of LHPC have been reported. Although one case of LHPC in the sinonasal region was briefly reported, this is the first case in the head and neck region with detailed clinicopathologic features and molecular analysis of this entity.

Definition of a Region of Loss of Heterozygosity at Chromosome 11q23.3-25 in Head and Neck Squamous Cell Carcinoma Using Laser Capture Microdissection Technique

To date, loss of heterozygosity (LOH) studies on HNSCC have had limited success in identifying a confined region of loss on chromosome 11q partially due to the heterogeneous nature of tumor tissue examined. Additionally, little is known about the role of the 11q allelic deletion in HNSCC tumorigenesis and current reports are conflicting. The aim of this study was to better define LOH at distal 11q by using combination of a pure cell population procured by laser capture microdissection (LCM) and subsequent sensitive PCR amplification of polymorphic microsatellites. This study analyzed HNSCC for LOH using a panel of 5 microsatellite markers spanning 11q23-25. Thirty-four paired DNA samples from tumor and autologous normal tissue were harvested by LCM technique to ensure a pure cell population for PCR amplification. Approximately 2000 to 3000 cells were procured from each sample. Twenty-one of 34 cases(62%, P < 0.001) showed LOH on at least one of the loci examined. The highest frequency of LOH was found at the 11q23.3-25 segment, with 44% at marker D11S968 and 35% at marker D11S1316. A distinct novel region of frequent LOH at 11q23.3-25, defined by D11S1316 and D11S968, was identified. No allelic loss was found in any normal squamous tissue samples. To study LOH in HNSCC, combination of pure cell population procurement by LCM and sensitive PCR provides a more accurate approach than the conventional method using a bulk of heterogeneous tissue. A novel region of LOH at 11q23.3-25 was defined. LOH in this region may harbor putative tumor suppressor gene(s) critical for HNSCC. Furthermore, these allelic losses were not found in any non-neoplastic squamous tissue samples, clarifying prior discrepant data.

Molecular Prognosticators and Genomic Instability in Papillary Thyroid Cancer

Objectives/Hypothesis: Tumor progression has been attributed to the accumulation of DNA damage concurrent with selection of advantageous mutations; this DNA damage may result from failure to maintain genomic integrity or from susceptibility to carcinogens. Glutathione S‐transferases (GSTs), enzymes that metabolize many carcinogens, may play a role in preserving genome integrity. The objectives of this study are to assess the relationship of GST genotypes with prognosis, clinicopathologic parameters, and genomic instability in papillary thyroid cancer.

Erratum: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: A consensus statement (Annals of Surgical Oncology 14 (128-133)DOI: 10.1245/s10434-006-9185-7)

J. Esquivel, R. Sticca, P. Sugarbaker, E. Levine, T. D. Yan, R. Alexander, D. Baratti, D. Bartlett, R. Barone, P. Barrios, S. Bieligk, P. Bretcha-Boix, C. K. Chang, F. Chu, Q. Chu, S. Daniel, E. deBree, M. Deraco, L. Dominguez-Parra, D. Elias, R. Flynn, J. Foster, A. Garofalo, F. N. Gilly, O. Glehen, A. Gomez-Portilla, L. Gonzalez-Bayon, S. Gonzalez-Moreno, M. Goodman, V. Gushchin, N. Hanna, J. Hartmann, L. Harrison, R. Hoefer, J. Kane, D. Kecmanovic, S. Kelley, J. Kuhn, J. LaMont, J. Lange, B. Li, B. Loggie, H. Mahteme, G. Mann, R. Martin, R. A. Misih, B. Moran, D. Morris, L. Onate-Ocana, N. Petrelli, G. Philippe, J. Pingpank, A. Pitroff, P. Piso, M. Quinones, L. Riley, L. Rutstein, S. Saha, S. Alrawi, A. Sardi, S. Schneebaum, P. Shen, D. Shibata, J. Spellman, A. Stojadinovic, J. Stewart, J. Torres-Melero, T. Tuttle, V. Verwaal, J. Villar, N. Wilkinson, R. Younan, H. Zeh, F. Zoetmulder, and G. Sebbag