Tahseen Al-Saleem

MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02

PURPOSE MDM2 regulates p53, which controls cell cycle arrest and apoptosis. Both proteins, along with Ki-67, which is an established strong determinant of metastasis, have shown promise in predicting the outcome of men treated with radiation therapy (RT) with or without short-term androgen deprivation (STAD). This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02. PATIENTS AND METHODS Adequate tissue for immunohistochemistry was available for p53, Ki-67, and MDM2 analyses in 478 patient cases. The percentage of tumor nuclei staining positive (PSP) was quantified manually or by image analysis, and the per-sample mean intensity score (MIS) was quantified by image analysis. Cox regression models were used to estimate overall mortality (OM), and Fine and Grays regressions were applied to the end points of distant metastasis (DM) and cause-specific mortality (CSM). Results In multivariate analyses that adjusted for all markers and treatment covariates, MDM2 overexpression was significantly related to DM (P = .02) and OM (P = .003), and Ki-67 overexpression was significantly related to DM (P < .0001), CSM (P = .0007), and OM (P = .01). P53 overexpression was significantly related to OM (P = .02). When considered in combination, the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points (P < .001 for DM, CSM, and OM). CONCLUSION Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and, if validated, could be considered for risk stratification of patients with prostate cancer in clinical trials.

Promoter Hypermethylation of the PALB2 Susceptibility Gene in Inherited and Sporadic Breast and Ovarian Cancer

The partner and localizer of BRCA2 (PALB2) gene was recently identified as a BRCA2-interacting protein and subsequently shown to be a Fanconi anemia gene (FANCN). Disease-associated point mutations resulting in protein truncation have been found in BRCA1/2 mutation-negative breast cancer families identifying PALB2 as a susceptibility gene for breast cancer. Aberrant promoter hypermethylation is a mechanism of inactivation of many tumor suppressor genes, including BRCA1 and p16(INK4a), in breast and ovarian cancer. We therefore investigated the methylation status of a 1512 bp typical CpG island located in the promoter and exon 1 region of the PALB2 gene in 130 sporadic and familial breast and ovarian primary tumors, 9 cell lines, and 10 normal cell specimens. We found two primary breast tumors from BRCA2 mutation carriers, four sporadic primary breast tumors, and four sporadic primary ovarian tumors showed hypermethylation of the core promoter region of PALB2. All 10 normal tissue DNA had an unmethylated PALB2 promoter region. Quantitative real-time reverse transcription-PCR showed PALB2 expression to be reduced 28-fold in primary breast tumor with PALB2 promoter hypermethylation compared with matched normal breast tissue RNA. Aberrant promoter hypermethylation of PALB2 is more frequent than the reported level of PALB2 point mutations in breast tumors from BRCA1/2-negative families and is similar to the frequency of BRCA1 hypermethylation in inherited and sporadic breast and ovarian cancers.

Alpha heavy chain disease (report of 18 cases from Iraq).

The clinical and pathological features of 18 new patients with alpha heavy chain disease seen at two referral centres in Baghdad, Iraq, are described. The series included 14 males and four females ranging in age from 14 to 47 years. Almost all patients presented because of long-standing abdominal pain and diarrhoea. The tissue diagnosis and extent of the disease were established at laparotomy in most patients. Peroral jejunal biospy was used in a number of patients, mainly for follow-up. The serological abnormality was confirmed by immunoselection technique. Most of the patients had extensive thickening of the bowel wall and/or tumour masses of the small intestine and mesenteric nodes. Histopathological sections showed muscularis. Preliminary results of the treatment, including two long remissions, are reported. In general, our observations agree with those made by other authors, mostly from the Middle East and Africa. We believe that a high index of clinical suspicion, routine use of the immunoselection, and recognition of the early pathological changes may hopefully lead to the detection of more cases before the frank neoplastic phase of the disease.

Clinical and pathologic subtypes of primary intestinal lymphoma. Experience with 132 patients over a 14-year period.

Primary lymphomas of the small intestine (PIL) show definite racial and geographic distribution. Clinical and laboratory data on 132 patients with PIL treated and followed up over a 14‐year period in Baghdad, Iraq, are presented. Based on the pattern of involvement of the bowel and the histopathologic appearance of the tumor, the patients can be divided into three main groups. Ninety‐seven patients had diffuse lymphoplasmacytic infiltration affecting large segments of the upper bowel. Abdominal pain, anorexia, weight loss, diarrhea, malabsorption, and clubbing of the fingers are the most common clinical findings. The barium appearance of the small intestine and peroral jejunal biopsy specimens are abnormal in nearly all cases. This clincopathologic entity has been referred to in the literature as Mediterranean lymphoma (ML). Ten of 34 patients tested had free alpha‐heavy chain in the serum. Twenty‐three cases had other “Western” variants of lymphoma (18 lymphocytic and 5 plasmacytic). The lesions were localized, occurring most frequently in the lower ileum or ileocecal area. The most common presentation was intestinal obstruction. Twelve children had Burkitts lymphoma (BL), presenting most commonly with abdominal masses and/or intestinal obstruction. These patients responded poorly to cyclophosphamide, and the disease disseminated early and extensively. None of the patients with the localized lymphomas or BL had free alpha chain in the serum.

Malignant lymphoma of the small intestine in Iraq. (Middle east lymphoma)

Thirty cases of malignant lymphoma involving the small bowel were studied. It seems that this condition is particularly prevalent in the Middle East. Most frequently, it involves the proximal parts of the small bowel in a diffuse form, resulting in malabsorption syndrome. Histologically, they are poorly differentiated lymphocytic and/or histiocytic. Further studies may reveal more interesting aspects of this entity.

Clinical significance of performing immunohistochemistry on cases with a previous diagnosis of cancer coming to a national comprehensive cancer center for treatment or second opinion.

Immunohistochemistry (IHC) is an important adjunctive test in diagnostic surgical pathology. We studied the clinical significance and outcomes in performing IHC on cases with a previous diagnosis of cancer who are coming to the Fox Chase Cancer Center (FCCC), a National Cancer Institute designated National Comprehensive Cancer Center (NCCC), for treatment and/or second opinion. We reviewed all the outside surgical pathology slide review cases seen at the FCCC for 1998 and 1999 in which IHC was performed. Cases were divided into the following: confirmation of outside diagnoses without and with prior IHC performed by the outside institution (groups A and B, respectively) and cases with a significant change in diagnosis without and with prior IHC performed by the outside institution (groups C and D, respectively). During 1998 and 1999, 6678 slide review cases were reviewed at the FCCC with an overall significant change in diagnosis in 213 cases (3.2%). IHC was performed on 186 of 6678 (2.7%) slide review cases with confirmation of the outside diagnosis in 152 (81.7%) cases and a significant change in diagnosis in 34 (18.3%) cases. Patient follow-up was obtained in 32 of 34 (94.1%) cases with a significant change in diagnosis (groups C and D), which confirmed the correctness of our diagnosis in 26 of 27 cases (96%; in five cases follow-up was inconclusive). We repeated the identical antibodies performed by the outside institutions in group D (37 antibodies) and group B (133 antibodies) with different results in 48.6% and 13.5%, respectively (overall nonconcordance 21.2%). In group D additional antibody tests beyond that performed by the outside institution were needed in 88.8% of cases to make a change of diagnosis. In the setting of a NCCC, reperforming and/or performing IHC on cases with a previous diagnosis of cancer is not a duplication of effort or misuse of resources. Repeating and/or performing IHC in this setting is important in the care and management of patients with cancer.

Sub-acute intestinal obstruction by Strongyloides stercolaris

Strongyloides stercolaris infestation is rather rare in Iraq. Individuals with infection confined to the intestinal tract are often asymptomatic. Symptoms include abdominal pain, diarrhea, weight loss and other non-specific complaints. The diagnosis depends upon repeated examination of stool and duodenal aspirate. Two cases presenting as sub-acute intestinal obstruction and mimicking primary intestinal lymphoma (PIL) on presentation are presented. Differentiation between the two conditions regarding presenting features, barium studies and pathology are discussed.

Primary intestinal lymphoma in Iraqi children.

Primary intestinal lymphomas (PIL) include a number of interesting clinical and pathological subtypes with distinct geographic, socioeconomic and age distribution patterns. This report describes clinical and pathologic features of 37 Iraqi children with PIL seen 1965-1983. Three distinct groups were recognized: Mediterranean lymphoma, 11 patients, characterized by diffuse involvement of the proximal bowel; commonly presents with abdominal pain, diarrhea and malabsorption; Burkitts lymphoma, 13 patients, characterized by localized tumor in the distal ileum or ileocecal region; commonly presents with intussusception, abdominal tumor and pain, and Non-Burkitts lymphoma, 13 patients, usually occurs as localized tumors in the distal ileum; commonly presents with abdominal tumor, pain and intestinal obstruction.

Carcinoma of the Pancreas in Iraq

This paper presents clinical observations on 130 patients with carcinoma of the pancreas, including 19 with periampullary cancer, the first large study of this disease in Iraq. All of the patients were admitted to the First (one of three) Surgical Unit of the University of Baghdad Teaching Hospital (the Medical City) during the period 1965-1977. The diagnosis and extent of disease were confirmed surgically in all patients. The clinical presentation, histopathologic characteristics, and prognostic features of the disease in Iraq seem no different from those seen in other parts of the world. Though relatively uncommon (1.4% of all male and 1.2% of all female cancers in the Baghdad Cancer Registry), cancer of the pancreas is the second most common tumor of the digestive system, next to that of the stomach.

MP92-01 PD-1 EXPRESSION ON CLASSICAL MONOCYTES (CM) IS AN INDEPENDENT PREDICTOR OF CANCER SPECIFIC SURVIVAL IN CLEAR CELL RENAL CARCINOMA (CCRCC)

genetic counseling, Klinefelter syndrome (3.6%) who underwent testicular sperm extraction (no men with Klinefelter syndrome had a positive YCM assay), and men with chromosomal abnormalities of the Y chromosome (1.9%) who chose donor sperm or adoption. Sequential testing for karyotype first and then YCM, results in 9.8% of men savings of