Expression of DNA mismatch repair proteins hMSH2 and hMLH1 and the cyclin G1 inhibitor, p21(waf1/cip1) in pediatric tumors: correlation with response to therapy.

The expression of the DNA mismatch repair proteins hMSH2 and hMLH1 and p21(waf1) the cyclin G1 inhibitor, may determine response of adult cancers to anti-cancer drugs, that include alkylating agents and platinum-based drugs. The role of DNA mismatch repair proteins (hMSH2 and hMLH1) and p21(waf1) in pediatric tumor responses to chemotherapy and irradiation is described in the present study of 23 pediatric solid cancers (4 wilms' tumors, 9 neuroblastomas, 3 hepatoblastomas, 3 lymphomas and 4 sarcomas) using immunohistochemical methods. Immunostaining was scored for intensity (0-3) and extent (0-3). Most tumors stained strongly for hMSH2 and weakly or negative for hMLH1. All the hMLH1 negative tumors (1 wilms', 1 hepatoblastoma, 1 sarcoma, 2 lymphomas and 2 neuroblastomas) achieved complete response. p21(waf1) negative and positive tumors achieved relatively similar treatment response. The results suggest that the expression of DNA mismatch repair proteins hMLH1 and hMSH2, and p21(waf1) do not influence individual cancer responses to treatment and the results may reflect the use of multiple drugs and irradiation that cause many different types of DNA damage.

Successful chelation therapy in a case of neonatal iron overload following intravascular intrauterine transfusion.

OBJECTIVE: We report a newborn infant who was successfully treated with chelation therapy having developed severe liver disease secondary to iron overload following multiple intrauterine, intravascular transfusions (IVTs). STUDY DESIGN: Case report with review of the literature. RESULTS: An infant was born at 33 weeks' gestation having received multiple IVTs for severe rhesus hemolytic disease. At birth there was severe anemia with hydrops and ascites. Severe liver disease was present with portal hypertension, coagulopathy and abnormal liver enzymes. A liver biopsy showed histologic features consistent with iron overload. The serum ferritin was in excess of 4000 micrograms/l. A 7-week course of deferoxamine resulted in a marked reduction in ferritin levels and significant improvement in liver function. CONCLUSION: The possibility of neonatal iron overload following multiple IVTs should be borne in mind. Successful chelation therapy is possible in such cases.

Sialyl-Lewis-X, Gleason grade and stage in non-metastatic human prostate cancer.

Early stage prostate cancers are now commonly encountered because of widespread use of screening tools. Increased cancer cell proliferation, and expression of sialyl Lewis could be important as predictors of clinical behaviour and survival in addition to histologic grade. In this study, the expression of sialyl-LewisX (sLeX) was determined by immunohistochemical methods in 38 routinely processed prostate biopsies and transurethral resections preceding radical prostatectomies for organ confined prostate cancers. Histologic grades were determined from pathologic reports and divided into two (2) groups; low grade (Gleason score 2-4) and medium grade (Gleason score 5-7). Tumour stages were based on radical prostatectomy reports and 29 were T2 and 9 were T3. SLeX was positive in 10 of 14 (71.4%) low grade and 14 of 24 (62.5%) medium grade cancers; 22/29 (75.9%) T2 and 8/9 (88.9%) T3 were sLeX positive; 1 of 15 (7.2%) low grade and 5 of 24 (20.8%) medium grade were strongly positive (3+) or overexpressing sLeX. Overexpression of sLeX was a feature of medium grade cancer, suggesting that localized prostate cancers with increased potential for progression and metastasis exist in the clinically non-metastatic group.

Expression of proliferating cell nuclear antigen in node-negative human prostate cancer.

Cancer cell proliferation could be an important predictor of clinical behavior and survival in node-negative prostate cancers. Proliferating cell nuclear antigen (PCNA; PC10) immunostaining was determined in 38 prostate biopsies and transurethral resections in clinically organ confined prostate cancers. 14 of the prostate cancers were Gleason score 2-4 and 24 were Gleason score 5-7. 29 were stage T2 and 9 were stage T3. Gleason score 2-4 cancers had a mean PCNA of 7.08 (s.d 5.1); Gleason score 5-7 had a mean PCNA of 11.42 (s.d 7.7), Stage T2 cancers had a mean PCNA of 8.007 (s.d 6.13) and stage T3 cancers had a mean PCNA of 12.7 (s.d 8.49). 21.4% of Gleason score 2-4, 12.5% of Gleason score 5-7, 10.7% of stage T2 and 10% of stage T3 had mean PCNA counts of twice their mean values. 4/24 (16.67%) of Gleason score 5-7 and 28.57% of stage T3 cancers had total PCNA counts > 20/2hpf suggesting high counts are indices of progression.

A, B, H, and Lewis-a and Lewis-b blood group antigens in human breast cancer: correlation with steroid hormone receptor and disease status.

Estrogen (ER) and progesterone (PR) hormone receptor status and levels were correlated with blood group antigen (A, B, H, Lewis-a and Lewis-b) expression in 48 cases of human breast cancer. Reduced expression of all the blood group antigens was observed with statistically significant reductions for H, Lewis-a and Lewis-b (P < 0.05). The proportions of ER- and PR-positive breast cancers staining for Lewis-b were greater than in hormone-receptor-negative cancers but the differences were not significant. The loss of Lewis-b antigen in breast cancer increased with tumor grade but did not correlate with axillary lymph node metastases. Loss of Lewis-b antigen is probably not a predictor of local recurrence and survival in the short period of observation. We conclude that the loss of H, Lewis-a and, especially, Lewis-b in breast cancer reflects the invasiveness of breast cancer and that Lewis-a and b expression is probably only marginally and not significantly affected by steroid hormone receptor status and levels.

Lewis blood group antigens (a and b) in human breast tissues. Loss of Lewis-b in breast cancer cells and correlation with tumor grade.

The Lewis blood group antigens (Lewis-a [Lea] and Lewis-b [Leb]) and their precursors are present on various normal human epithelial cell surfaces. The authors examined 35 benign and malignant human breast lesions using mouse monoclonal antibodies to synthetic Lea and Leb carbohydrate antigens. Normal breast lobular and ductal epithelium and benign breast lesions showed Leb staining but only occasional Lea staining. In invasive ductal carcinomas of breast, of all grades, a loss of Leb antigen staining was found in 80% of the breast cancer cases. This reduced Leb antigen expression increased with the grade of malignancy. Therefore, the loss of Leb blood group antigens on breast cancer cell surfaces may suggest altered fucosylation patterns in malignant cells and reflect the degree of malignancy and/or invasiveness.

Fine structural alterations in radiofrequency energy-induced lesions in dog hearts: possible basis for reduced arrhythmic complications.

OBJECTIVE: To define fine structural changes in canine myocardium due to radiofrequency energy; to compare these changes with those due to direct current shock; and to determine if differences found can explain the reduction in arrhythmic complications observed following the use of radiofrequency energy. ANIMALS: Ten mongrel dogs were used for radiofrequency energy and seven for direct current shock experiments. DESIGN: Twenty-five Joules of direct current and 150 to 300 J of radiofrequency energy were delivered via catheters to the myocardium of anesthetized dogs. The endomyocardium was excised and processed for electron microscopy. MAIN RESULTS: The endomyocardial damage produced by radiofrequency energy and direct current shock was similar at the light microscopic levels. Ultrastructurally, the myocyte changes were similar but the supporting vasculature was better preserved in the direct current-damaged myocardium. CONCLUSION: The lack of vascular preservation in radiofrequency energy-induced damage compared to direct current shock myocardial damage may provide a morphological background for the reduced arrhythmic complications noted.

Correlation of blood group antigen expression and oncogene-related proteins in malignant prostatic tissues.

The use of multiple tumor markers could better predict the behavior of malignant tumors. In prostate cancer, there are no reliably predictive markers for metastatic behavior but the histologic grade and clinical stage of tumor do influence prognosis. We have determined the expression of blood group antigens A, B, H, Lewis-a and Lewis-b and the proto-oncogene proteins v-erbB, c-fos and v-H-ras in both benign and malignant prostate tissues by immunohistochemistry. We determined the relationship between these markers and the grade of malignancy and by inference, clinical behavior. There was reduced expression of blood group antigens A, Lewis-a and Lewis-b in all grades of prostatic adenocarcinoma. We also found that the expression of v-erbB was greater in tumors of high grade. We suggest that loss of blood group antigens may be correlated with elevated v-erbB oncoprotein expression (related to epidermal growth factor receptor) and increasing grade of prostatic malignancy.

Monomorphic adenoma of the nasal septum in a newborn (case report and ultrastructural findings).

Salivary gland type adenomas of the nasal septum are rare tumors in adults and even rarer in children. There has been no previous report of such a tumor in a neonate. We have described a tumor of the nasal septum whose light and electron microscopic appearances are consistent with an origin from minor salivary gland or nasal mucous glands. Ultrastructural findings presented do not suggest an origin from the embryonic organ of Jacobson (vomeronasal organ). The biological behaviour of this tumor in the neonate is unknown. A study of similar cases will be necessary to elucidate the incidence and natural history of intranasal adenomas in the neonate.

Malignant transformation in an anal condyloma acuminatum.

A 61-year-old man had malignant transformation of an anal condyloma acuminatum, demonstrated by light and electron microscopic studies. Intranuclear virus-like particles were seen in the benign condylomatous koilocytotic cells but these were absent in the malignant cells. Multinucleation, syncytial giant cells and nuclear atypia in a condyloma acuminatum are considered features of in-situ carcinomatous change. Anal condyloma acuminatum requires wide excision and thorough examination of anorectal canal in order to exclude hidden disease, which will predispose to recurrence. Homosexuality is considered a predisposing factor. The authors stress the importance of histopathologic examination of all anorectal warts to exclude malignant change.