Expression of p27(Kip1) and bcl-2, cigarette smoking, and colorectal cancer risk.

Although a positive association between cigarette smoking and colorectal adenoma development is consistently found, the association with colorectal cancer remains controversial. We evaluated the potential roles of p27(Kip1) and bcl-2 protein expressions in conjunction with cigarette smoking exposure and colorectal cancer risk in a hospital-based case-control study. A total of 163 colorectal cancer patients from Roswell Park Cancer Institute and Buffalo General Hospital and 326 healthy controls responded to a standardized questionnaire on colorectal cancer risk factors including detailed information on their history of cigarette smoking; 110 of the patients' tumours were available for immunohistochemical analysis of p27(Kip1) and bcl-2 protein overexpression. An avidin-biotin immunoperoxidase procedure was used to determine expression after incubation with mouse monoclonal p27(Kip1) and mouse monoclonal bcl-2 antibodies, respectively. A statistically significant trend for total pack-years of smoking was found when p27(Kip1) positive cases were compared with p27(Kip1) negative cases (trend test, p = 0.007). Although a weak inverse association was observed with smoking exposure among p27(Kip1) negative tumour cases in comparison to controls, a significant dose-response association was seen with p27(Kip1) positive tumours. The relative risk of developing a p27(Kip1) positive tumour was estimated to be 1.17 (95% CI 0.54-2.54) for those with less than 20 pack-years, 1.95 (95 % CI 0.95-3.97) for those with 20-39 pack-years, and 2.25 (95% CI 1.14-4.45) for those with greater than 39 pack-years of smoking exposure (trend test, p = 0.009) when compared with controls. When cases with bcl-2 expression were compared with cases without bcl-2 expression, suggestion of a trend was also observed with pack-years smoked (trend test, p = 0.09). In our study of 110 patients with sporadic colorectal cancer and 326 controls, we observed differences in associations between cigarette smoking and expressions in p27(Kip1) and bcl-2. Our data suggest that bcl-2 overexpression (or a bcl-2 dependent pathway) is associated with cigarette smoking in the development of colorectal cancer, whereas a loss of p27(Kip1) expression is not. These associations indicate that there is aetiological heterogeneity in colorectal cancer development, and that they can indirectly allude to where these changes in protein expression occur in the adenoma-carcinoma sequence (i.e. early versus late events).

Prognostic significance of p53, PCNA, and c-erbB-2 in endometrial enocarcinoma.

Previous studies of oncogenes, tumor suppressor genes, and proliferation markers in endometrial adenocarcinoma have obtained conflicting results regarding the usefulness of these markers in predicting prognosis. This study examined p53, PCNA, and c-erbB-2 immunohistochemically to clarify the relationship of these markers to each other and to FIGO stage, myometrial invasion, and survival. We studied 64 cases of endometrial carcinoma, treated between 1988 and 1995, for overexpression of p53, percentage of PCNA expression (PCNA index), and c-erbB-2 cytoplasmic membrane staining. Thirty-two percent of tumors expressed p53, 39% displayed a PCNA index of > = 25%, and 69% expressed c-erbB-2. p53 overexpression was significantly associated with stage (p=0.027), PCNA index > = 25% (p=0.005), c-erbB-2 expression (p=0.018), and vital status (p=0.04). PCNA index > = 25% was associated with stage (p=0.008), myometrial invasion (p=0.008), and c-erbB-2 expression (p=0.05), and weakly associated with vital status (p=0.07). No associations were observed for c-erbB-2 with stage, invasion, or vital status. There was some suggestion of a decreased survival in patients whose tumors overexpressed p53 (Log Rank; p=0.09) or had a PCNA index > = 25% (Log Rank; p=0.13). Additional, larger studies are needed to evaluate the prognostic value of PCNA and p53 expression in endometrial adenocarcinoma.

Aspirin use and p53 expression in colorectal cancer.

p53 protein overexpression indicates loss of tumor suppressor activity and is the most common genetic alteration in colorectal neoplasms. Epidemiologic and experimental studies suggest that regular use of aspirin may reduce colorectal cancer risk. We set out to determine whether p53 overexpression of the colorectum was associated with a patient's history of aspirin use. Self-administered questionnaires, including information on aspirin use, were obtained from 163 patients with nonfamilial colorectal cancer and from 326 healthy controls. Nuclear p53 protein overexpression using anti-p53 CM-1 polyclonal antibody was observed in 44.8% (73/163) of patients' tumors. A nonsignificant inverse association was observed between use of aspirin and colorectal cancer. Compared with that for nonusers, the odds ratio (OR) for individuals who took aspirin at least twice weekly was 0.68 (95% confidence interval [95% CI]: 0.39-1.18). The odds ratio for those individuals who used aspirin for less than 5 years was 0.54 (95% CI: 0.24-1.23), and 0.80 (95% CI: 0.42-1.51) for those who used aspirin for 5 years or more, when compared with nonusers. An inverse association of regular aspirin use (two times per week or more) was found both for cases with p53 overexpression (OR: 0.79; 95% CI: 0.39-1.59), and for cases without p53 overexpression (OR: 0.56; 95% CI: 0.25-1.22). There was little evidence of a difference in the effect of aspirin use on cancer risk between cases with and without p53 overexpression, even after adjustment for potential confounders.

Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer.

Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent. This inconsistency may be due in part to the biological heterogeneity of colorectal tumors. A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma. Fifty per cent (32/64) of colorectal tumors displayed nuclear over-expression of p53 protein. Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02). In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10). These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer.

Familial and nutritional risk factors for p53 overexpression in colorectal cancer.

Although familial and dietary factors are recognized as important risk determinants for colorectal tumorigenesis, the specific causes of colorectal cancer remain unclear. Studies of p53 genetic alterations have provided clues concerning the etiology of many cancers. This study was designed to determine whether overexpression of the p53 protein is associated with familial and dietary risk factors. Epidemiological data were obtained from 163 colorectal cancer cases and 326 healthy controls. Tumors of all patients were analyzed immunohistochemically for p53 overexpression using an avidin-biotin immunoperoxidase procedure and polyclonal anti-p53 antibody CM1. Of patient tumors, 44.8% showed p53 nuclear reactivity. Colorectal cases versus controls were three times more likely to report a family history of colorectal cancer [odds ratio (OR), 3.12; 95% confidence interval (CI), 1.77-5.52]. Only cruciferous vegetables exhibited a significant inverse association (OR, 0.59; 95% CI, 0.34-1.02; trend test, P = 0.03) for the highest versus lowest quartiles. Both meat and beef displayed an elevated increase in risk. When cases with p53 overexpression (p53 positive) were compared with cases without p53 overexpression (p53 negative), etiological heterogeneity was suggested for family history of colorectal cancer (OR, 0.39; 95% CI, 0.16-0.93), cruciferous vegetables (trend test, P = 0.12), and beef consumption (trend test, P = 0.08). To estimate the individual relative risks for p53-dependent and p53-independent pathways, each p53 subtype was compared with controls. Cruciferous vegetables exhibited a significant association (OR, 0.37; 95% CI, 0.17-0.82; trend test, P = 0.03) when p53 positive cases were compared with controls. When p53 negative cases were compared with controls, a significant increase in risk was observed for family history of cancer (OR, 4.46; 95% CI, 2.36-8.43) and beef (OR, 3.17; 95% CI, 1.83-11.28; trend test, P = 0.006). The p53 (positive) dependent pathway was characterized by an inverse association with cruciferous vegetables, and p53-independent tumors were characterized by family history and beef consumption. These data may indicate the significance of linking epidemiology and molecular biology in assessing specific etiological pathways.

The relationship between smoking exposure and p53 overexpression in colorectal cancer.

Although epidemiological studies of the relationship between cigarette smoking and colorectal cancer risk have been equivocal, a positive association is consistently found for colorectal adenoma development. We performed an epidemiological study to determine whether p53 protein overexpression, in tumours obtained at the time of resection, is associated with cigarette exposure in colorectal cancer. A total of 163 colorectal cancer cases and 326 healthy controls responded to a standardised questionnaire on colorectal cancer risk factors including detailed information on their history of cigarette smoking. All patients' tumours were analysed immunohistochemically for p53 overexpression using an avidin-biotin immunoperoxidase procedure and polyclonal anti-p53 antibody CM1. Comparison of colorectal cases with controls revealed an elevated risk for ex-smokers (OR = 1.34, 95% CI 0.85-2.12) and current smokers (OR = 1.13, 95% CI 0.63-2.02) when compared with non-smokers. No dose-response relationship was found for total pack-years of smoking (trend test: P = 0.19). However, a trend for total pack-years of smoking was found when p53-positive cases were compared with p53-negative cases suggesting aetiological, heterogeneity (trend test: P = 0.06). Estimating the individual relative risk of developing a p53-positive tumour relative to controls showed no associations for smoking status or total pack-years of smoking. However, when p53-negative cases were compared with controls, an elevated risk was found for ex-smokers (OR = 1.84, 95% CI 1.00-3.37) and current years of smoking (trend test: P = 0.03). Colorectal tumours developing through p53-positive dependent pathways were not associated with smoking exposure. A significant increase in risk was observed for the p53-negative independent pathway with smoking. p53 overexpression appears to be associated with smoking exposure in colorectal cancer.

Ovarian endodermal sinus tumor associated with pregnancy: review of the literature.

Endodermal sinus tumor is the second most common malignant germ cell tumor of the ovary and its reported concurrence with pregnancy is extremely rare. This report is the 10th case of endodermal sinus tumor associated with pregnancy and also reviews the previous literature regarding the subject.

Prostatic malakoplakia associated with prostatic adenocarcinoma and multiple prostatic abscesses.

Two cases of prostatic malakoplakia are presented. One case was associated with adenocarcinoma of the prostate and the second was noted with multiple prostatic abscesses. The literature on malakoplakia of the prostate is reviewed.

Papillary adenoma of the prostatic urethra.

Six patients with papillary adenoma of the prostatic urethra are described. Their ages ranged from 39 to 70 years old. Two of them showed evidence of clinical recurrence 1 year after treatment. The pathological features as well as the immunohistochemical demonstration of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) are illustrated. A brief review of the literature is discussed with special emphasis on the histogenesis and nature of this lesion.

Immunohistochemical demonstration of prostate-specific antigen in metastases with the use of monoclonal antibody F5.

With the use of a murine monoclonal antibody (F5), a panel of metastatic tumors was evaluated for the expression of prostate-specific antigen (PA) under immunoperoxidase staining procedures. Specimens studied included 25 of prostatic origin and 73 originating from nonprostatic primary sites. Regardless of the site of dissemination or the malignancy grade, all metastases from the prostate were antibody-reactive. In contrast, nonprostatic metastases were negative in each case, including those originating from other genitourinary neoplasms. Thus, PA expression as detected with monoclonal antibody F5 is a stable characteristic of disseminated prostatic tumors.

Functional and ultrastructural effects of nontypeable Haemophilus influenzae in a hamster trachea organ culture system.

A hamster trachea organ culture system was utilized to evaluate quantitatively the effects of a strain of nontypeable Haemophilus influenzae (NTHI) and culture supernatants of the same strain on ciliary activity. Tracheal explants were maintained in organ culture for 96 to 144 h and ciliary activity was observed daily with an inverted microscope. Explants continuously exposed to a strain of NTHI had a progressive decline in ciliary activity which was significantly lower than uninfected controls evaluated concomitantly by 48 h of exposure and thereafter. Histologic studies revealed a progressive degeneration of mucosal cells and exfoliation of ciliated cells. Scanning electron microscopy showed little adherence of NTHI to the mucosal surface. Sterile broth cultures of NTHI and supernatants of organ cultures infected with the same NTHI strain had no adverse effect on ciliary activity. Infected tracheal explants treated with ampicillin 24, 48, or 72 h after continuous bacterial challenge had no significant decline in ciliary activity compared to controls. The lack of adherence and the histologic changes observed when hamster trachea cultures were infected with NTHI suggested a toxin might mediate the damage observed. Broth and organ culture supernatants, however, produced no damage. Therefore, further studies are needed to determine the role, if any, of a toxin in the production of damage to hamster tracheal explants by NTHI.

Arteriovenous malformations as a cause of gastrointestinal bleeding: the importance of triple-vessel angiographic studies in diagnosis and prevention of rebleeding.

Arteriovenous malformations of the gastrointestinal tract are a source of upper and lower gastrointestinal bleeding. We studied 40 patients with arteriovenous malformations. Eighteen percent had single lesions in either the distal transverse colon or the left colon (the angiographic distribution of the inferior mesenteric artery). Seventeen percent had concomitant colonic and extracolonic arteriovenous malformations. Only 6% of those who underwent surgery for removal of arteriovenous malformations rebled. We also studied the incidence of angiodysplastic lesions of the colon of 159 patients over the age of 55 with lower gastrointestinal bleeding; associated arteriovenous malformations were present in 21%. These data suggest: that to evaluate arteriovenous malformations as a cause of gastrointestinal bleeding, one must perform inferior and superior mesenteric and celiac angiography; the incidence of rebleeding is reduced when triple-vessel selective visceral angiography precedes surgical removal of arteriovenous malformations; and the incidence of associated arteriovenous malformations approaches that of diverticulosis in elderly patients with lower gastrointestinal bleeding.

Prostate cancer grading: the NPCP system.

The use of the NPCP grading system does not contradict the principle that an accurate prediction of tumor volume, presence, and extent of metastases, therapeutic response, and clinical behavior of prostate cancer cannot be entirely based on the grade of the disease at the time of initial diagnosis. The morphology of prostate cancer, like any other cancer, is probably no more than one of a group of parameters that are decisive for the prediction of the biology and clinical course of the disease. Nevertheless, the present data support the premise that the NPCP system of grading prostate cancer, among others, is a very helpful indicator of the extent and behavior of prostate malignancy. Table 6 illustrates the correlation between grades and stages of prostatic carcinoma that can be drawn from the preceding data.

Histologic grading of primary prostatic cancer: a new approach to an old problem.

A simple and objective system for grading prostatic carcinoma was evaluated in a retrospective analysis of 169 cases followed during a 16-year period. The system identified and separated 4 grades of increasing malignancy based on the combined evaluation of gland differentiation and nuclear anaplasia as separate but complementary factors. The system demonstrates significant correlation with mortality rates for each grade group. Retrospective evaluation of the extent of the disease at the time of initial diagnosis also indicates correlation between prostatic grades and clinical stages.

Antibodies to native DNA: detection by immunoperoxidase assay and determination of their immunoglobulin classes.

Antinuclear antibodies are almost always found in sera of patients with systemic lupus erythematosus. To differentiate antinuclear antibodies from antibodies to DNA in the recently described Crithidia luciliae assay, we developed an immunoperoxidase technique for detecting antibodies to native, double-stranded DNA and compared results by it with those by the Farr assay. Smears of cultured Crithidia luciliae were incubated with human sera, peroxidase-labeled anti-human IgG serum, and diaminobenzidine. The peroxidase stain was examined by conventional light microscopy, which facilitated differentiation between the kinetoplast and the nuclear staining. The Crithidia assay appeared to be specific for double-stranded DNA antibodies, seemed to be more sensitive than the Farr assay, and allowed us to determine the immunoglobulin classes of antibodies to native DNA. Some patients with systemic lupus erythematosus had only IgM or IgA antibodies to DNA.

Hamartomatous adiposity of thyroid gland.

A rare case of hamartomatous adiposity of the thyroid gland was found incidentally in a 73 year old white female with adenocarcinoma of the rectum. Pressure symptoms related to the goiter (120 gms) were the only manifestations noted. Extensive laboratory investigations failed to reveal any demonstrable functional abnormality of the thyroid gland.

Inflammatory fibrous histiocytoma: case report.

This report concerns a patient with inflammatory fibrous histiocytoma, who in contrast to previous reported cases, has had a long survival (20 years), without evidence of recurrent disease following treatment. An interesting but nonreproducible study was the development of leukemia in 2 of 3 Swiss strain mice following the intraperitoneal injection of a saline extract of the patient's tumor.