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Aromatase and cyclooxygenase-2 expression in endometrial polyps during the menstrual cycle.

OBJECTIVES: To study the changes in aromatase, Ki-67 and cyclooxygenase-2 (COX-2) expression during the menstrual cycle in both endometrial polyps and normal endometria. PATIENTS AND METHODS: Paraffin-embedded tissue samples from 118 premenopausal patients were submitted to immunohistochemistry for measurement of aromatase, COX-2 and Ki-67 expression. Fifty cases of endometrial polyps and 68 cases of disease-free endometrium were included. RESULTS: The presence of aromatase expression was significantly higher in endometrial polyps than in disease-free endometria. On the other hand, changes in COX-2 and Ki-67 expression followed a similar pattern during the menstrual cycle in both groups, expression peaking during the proliferative phase and falling during the late luteal phase. CONCLUSION: A significantly higher proportion of endometrial polyps express aromatase compared with disease-free endometrium; however, no correlation was found between aromatase expression and changes in either Ki-67 or COX-2 expression during the menstrual cycle.

Adult↗

Histological assessment of colorectal adenomas by size. Are polyps less than 10 mm in size clinically important?

OBJECTIVE: To define the relative risk of malignant transformation in colorectal adenomas less than 10 mm in diameter. DESIGN: Prospective study. SETTING: District general hospital, UK. SUBJECTS AND MATERIALS: 1228 polyps detected endoscopically in 445 patients over the 10-year period 1989-1999. MAIN OUTCOME MEASURES: Site, size, histological type and dysplastic grade of polyp. RESULTS: 657 of the 1228 polyps were adenomas: 281 (43%) tubular, 339 (51%) tubulovillous and 37 (6%) villous. In the 357 adenomas less than 10 mm in diameter, 11 (3%) were severely dysplastic and 2 carcinomas were detected, though neither was less than 5 mm in size. The relative risk of malignancy or severe dysplasia in adenomas of 10 mm or more compared with those of less than 10 mm was 3.8 (p < 0.0001). CONCLUSIONS: Although severe dysplasia and malignancy do occur in adenomas less than 10 mm in size, they are rare in lesions of less than 5 mm. We recommend routine destruction of all polyps 5 mm or more in size, though it is not essential to remove those of less than 5 mm if they are kept under surveillance.

Adenoma↗

Effect of prednisolone on cytokine synthesis in nasal polyps.

To investigate steroid effects on eosinophils and their associated cytokines in nasal polyps, we sampled nasal polyp tissue from 20 subjects during routine surgery. Freshley removed polyps were cut into small pieces and incubated in culture medium for 24 h in different concentrations of prednisolone (10(-2)-10(-6) mol/L). Cell viability was assessed by means of trypan dye exclusion of the supernatants. The number of eosinophils was quantified by means of cytocentrifuge smears stained by May-Giemsa-Grunwald stain. The cytokine protein content of interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured by ELISA technique in supernatants and in homogenates of nasal polyp tissue. Our results revealed a significant reduction in the number of eosinophils and total number of vital cells at concentrations of 10(-3) and 10(-2) mol/L. GM-CSF and IL-5 protein levels were significantly reduced in supernatants and in homogenates after treatment with prednisolone, whereas IL-3 synthesis was not diminished. Corticosteroid effects known to inhibit synthesis of eosinophil-associated cytokines could be measured in terms of a significant decrease in IL-5 and GM-CSF protein level as well as in a decrease in the number of vital cells.

Cell Survival↗

Laparoscopic resection of malignant gastric polyp-with a particular emphasis on localization by laparoscopic ultrasonography.

Adenomatous polyps of the stomach are rare and usually found on routine endoscopic examination. These polyps should be removed because of their potential for malignant transformation. Endoscopic polypectomy is the preferred treatment modality, but a laparotomy is required to resect large polyps. This study presents a case of a large gastric polyp containing carcinoma in situ that was successfully managed by laparoscopic gastrectomy. With the use of a novel technique, the tumor was localized by intraoperative laparoscopic ultrasonography. The patient had an excellent postoperative recovery, and follow-up endoscopy at 24 months revealed no recurrent tumor.

Adenoma↗

Histopathologic changes are not specific for diagnosis of gastric antral vascular ectasia (GAVE) syndrome: a review of the pathogenesis and a comparative image analysis morphometric study of GAVE syndrome and gastric hyperplastic polyps.

We studied the nonspecific nature of the histologic findings in the gastric antral vascular ectasia (GAVE) syndrome by using a morphometric comparison with common gastric lesions including hyperplastic polyps and gastritis. Five clinicopathologically confirmed cases of GAVE syndrome and 41 cases of gastric hyperplastic polyps were diagnosed during a 5-year interval at Summa Health Systems (Akron, Ohio). These cases, as well as 16 randomly selected cases of nonspecific gastritis and 9 normal gastric antral biopsy specimens, were evaluated. A semiquantitative comparison of the light microscopic findings believed to be essential in diagnosis of GAVE syndrome, including vascular hyperplasia, mucosal vascular ectasia, intravascular fibrin thrombi, and fibromuscular hyperplasia, was performed. Image analysis morphometric measures of the area ratio (vascular area/total biopsy area), mean vascular area, and number of ectatic vessels per square millimeter of tissue were performed on the CAS 200 Image Analyzer (Becton Dickinson, San Jose, Calif). By morphometric and statistical parametric analysis, several histopathologic variables, including area ratio, mean vascular area, mucosal vascular ectasia, and fibromuscular hyperplasia, did not confidently differentiate the histologic features of gastric hyperplastic polyp from those of GAVE syndrome, but did apparently differentiate GAVE syndrome from gastritis and normal gastric mucosa. The propensity of gastric hyperplastic polyps to undergo prolapse changes and prolapse as one proposed mechanism for development of the GAVE syndrome lesion probably accounts for this morphologic similarity. Specific diagnostic histopathologic changes probably do not exist for the GAVE syndrome.

Aged↗

Hyperplastic polyps of the gastric mucosa adjacent to gastroenterostomy stomas.

In two patients with functionally active, nonatrophic oxyntic gastric mucosa, hyperplastic polyps developed on the gastric side of Billroth II and Billroth I anastomoses. The polyp associated with the Billroth II procedure was almost circumferential, sparing only the lesser curvature. That associated with the Billroth I operation was on the anterior wall from lesser to greater curvature. The operations had been performed 11 years and ten years earlier for peptic ulcers of the gastroduodenal junction. The sites of polyp formation resembled those of experimental cancers in rats with Billroth I and Billroth II anastomoses, and of human cancer occurring 20 or more years after gastrojejunostomy for benign disease. This suggests that stomal carcinomas and hyperplastic polyps each result from the reflux of enteric contents into the stomach remnant.

Aged↗

Fruits, vegetables, and adenomatous polyps: the Minnesota Cancer Prevention Research Unit case-control study.

Although high vegetable intakes have been associated with a lower risk of colorectal cancer, this relation is less well established for the precursor lesions, adenomatous polyps. With a case-control design involving adenomatous polyp cases (n = 564), colonoscopy-negative controls who were polyp free at colonoscopy (n = 682), and community controls (n = 535), this 1991-1994 Minnesota Cancer Prevention Research Unit study investigated the relation between fruit and vegetable consumption and first incident adenomatous polyps. Dietary intake was assessed using a food frequency questionnaire. For women, adenoma risk was approximately halved in the highest versus lowest quintile of juice consumption (cases vs. colonoscopy-negative controls: odds ratio (OR) = 0.50, 95% confidence interval (CI): 0.27, 0.92; cases vs. community controls: OR = 0.56, 95% CI: 0.30, 1.06). The association was stronger for adenomas with moderate or severe dysplasia compared with mild dysplasia. Juice was not associated with adenoma risk in men. The results for fruits, vegetables, total fruits and vegetables, green leafy vegetables, and several botanically and phytochemically defined subgroups generally were not statistically significant. Because elevated vegetable consumption has been associated with a lower risk of colorectal cancer, vegetables may have a stronger role in preventing the progression of adenomas to carcinomas rather than in preventing the initial appearance of adenomas.

Adenomatous Polyps↗

Aberrant expression of nitric oxide synthase in human polyps, neoplastic colonic mucosa and surrounding peritumoral normal mucosa.

The expression of nitric oxide synthase (NOS) was studied by NAD(P)H diaphorase histochemical localization method in (i) individual cells of the normal colonic mucosa (n = 13) which served as control, (ii) colonic polyps (n = 14), (iii) colonic carcinoma (n = 20) and (iv) peritumoral mucosa (2 and 5 or 10 cm away from the tumor). Four of the tumor specimens had normal epithelium adjacent to the cancer, which thus served as an internal control. The expression of NOS activity in colon cancer was significantly reduced as compared to the control group of individuals (P < 0.004); undetectable in 25%, diminished in 45%, normal in 30%. On comparing the expression in normal mucosa and polyps there was a significant reduction of the expression in polyps (P < 0.027); undetectable in 14%, reduced in 35%, normal in 51%. When compared to the peritumoral mucosa at 2 and 10 cm the tumor showed a significant reduction in expression of NOS activity (P < 0.001 and P < 0.0001 respectively). There was no significant difference seen in the expression at 2 and 10 cm (P = 0.329). The peritumoral mucosa at a distance of 2 cm away from the tumor when compared to the control mucosa showed no significant difference (P = 1.000), although there is a tendency to a high normal expression of NOS activity in the mucosa at a distance of 2 cm. Similarly, there was no significant difference between the control mucosa and the peritumoral mucosa obtained at a distance of 10 cm (P = 0.383). The expression of NOS activity in all tissues examined was abolished by preincubation of tissue with the selective NOS inhibitor L-NMMA but not with D-NMMA. Our data showed extensive and significant reduction as identified by the NAD(P)H diaphorase method in the expression of NOS activity, thereby reflecting the activity of nitric oxide in colon cancer and colonic polyps. The generalized suppression of this activity, which precedes the onset of overt neoplasia, may be an important event in colon carcinogenesis. This aberrant expression could also be compatible with the selective advantage to either tumor promotion and metastatic progression or to tumoricidal activity.

Adenocarcinoma↗

Increased activities of thymidine kinase isozymes in human colon polyp and carcinoma.

Thymidine kinase (TK), the enzyme in the pyrimidine salvage pathway, and its isozymes were examined in 15 specimens of normal mucosa, 14 polyps and 14 carcinomas in human colon. The average TK activities in colon polyps and carcinomas were about 1.6 and 2.9 times that in normal colon mucosa, respectively. The colon TK isozymes were separated into 2 types by DEAE-cellulose column chromatography. The activity of the TK isozyme eluted with 0.1 M NaCl in buffer was 1.6-fold higher in colon polyp and 1.5-fold higher in colon carcinoma than that in normal colon mucosa. In colon carcinoma, but not colon polyp, the activity of the other isozyme eluted with buffer alone was increased to 5.1-fold that in normal tissues. As the activity of the latter isozyme was not affected by deoxycytidine triphosphate, it may be involved in DNA replication. The results suggest that increases in the activities in the former and latter TK isozymes may indicate tumorigenesis and carcinogenesis, respectively, in the human colon.

Adult↗

Effects of cumene hydroperoxide on adenosine diphosphate ribosyl transferase in mononuclear leukocytes of patients with adenomatous polyps in the colon.

We have studied the effects of plasma and of cumene hydroperoxide (CUM) on adenosine diphosphate ribosyl transferase (ADPRT) from mononuclear leukocytes (HML) of patients with colonic adenomatous polyps (n = 22), with colonic hyperplastic polyps (n = 5) and with neither type of polyp (controls) (n = 6). ADPRT was measured after incubation of HML with plasma alone (termed the plasma value), and with plasma plus CUM (50 microM) (the activated value); the difference elicited by CUM was termed the induced value. There was no significant difference in values between the control and hyperplastic polyp groups: these were combined for further analysis. The plasma (P = 0.038), activated (P = 0.009) and induced (P = 0.0024) values of the combined group all differed significantly from those of the adenoma group. At low exposures, CUM stimulated both ADPRT and unscheduled DNA synthesis and, at higher exposures, inactivated both. Pretreatment of HML with vitamin E protected against these effects of CUM, while pretreatment with diamide (which depletes GSH) accentuated the effects. This study demonstrates a differential reaction of ADPRT in patients harboring colonic adenomas and suggests that the origin of this difference may lie in cellular responses to oxidative stress.

Benzene Derivatives↗

Increased expression of cyclooxygenase-2 to -1 in human colorectal cancers and adenomas, but not in hyperplastic polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs can reduce the risk of colorectal cancer. Reportedly, mRNA expression of cyclooxygenase-2 (COX-2) is elevated in human colorectal cancers compared with accompanying normal mucosa. The present study was undertaken to establish a simple analytical procedure to quantify COX-2 expression levels and to characterize COX-2 expression levels in human colorectal cancers, adenomas and hyperplastic polyps. METHODS: The combination of PCR using common primers designed in the highly conserved regions and fluorescence-based single-strand conformation polymorphism (F-SSCP) analysis of the products is used for quantitative determination of the proportions of COX-2 mRNA in human colorectal cancers, adenomas, hyperplastic polyps and accompanying normal mucosa. RESULTS: The present F-SSCP analysis was a simple and powerful method for quantitative determination of the proportions of COX-2 mRNA. The proportion of COX-2 mRNA was higher in cancer tissues than in accompanying normal mucosa in 46 of the 50 cancers. There was no significant correlation between the increase of the COX-2 proportion and tumor location or stages. The enhanced COX-2 expression was also observed in colorectal adenomas. On the other hand, the proportion of COX-2 mRNA in hyperplastic polyps was not significantly different from that in normal mucosa. CONCLUSIONS: The proportion of COX-2 to COX-1 expression was elevated in most human colorectal cancers and adenomas, but not in hyperplastic polyps. Therefore, the increased proportion of COX-2 expression might be an early event in the carcinogenesis of colorectal cancer.

Adenoma↗

Epithelial blood group antigens in colon polyps. I. Morphologic distribution and relationship to differentiation.

The distribution patterns of epithelial blood group AB antigens (BG) in colon polyps of varying degrees of differentiation were studied by the mixed cell agglutination reaction. BG appeared in colon polyps if a certain degree of dedifferentiation was present. Two different distribution patterns were recognized: 1) association of BG with the secretory part of goblet cells with slight-to-moderate atypia and 2) association of BG with the whole cells in cases of pronounced dedifferentiation and loss of secretory activity. The second type resembled the distribution pattern of BG found previously in colon carcinomas. With respect to BG, the mucosa of colon polyps behaved similarly to embryonal colon mucosa. The detection of BG represents a useful method to assess objectively the degree of dedifferentiation in most colon polyps.

ABO Blood-Group System↗

Plasma carotenoids and the prevalence of adenomatous polyps of the distal colon and rectum.

In a case-control study, the authors investigated relations between plasma carotenoid concentrations and the prevalence of colorectal adenomatous polyps (precursors to colorectal cancer) in residents of Los Angeles County and Orange County, California, from 1991 through 1993. Plasma concentrations of six carotenoids were compared in 472 asymptomatic cases with a first-time diagnosis of at least one adenomatous polyp of the distal colon or rectum and 502 matched controls. Odds ratios adjusted for age, sex, smoking, alcohol intake, and energy, saturated fat, and fruit and vegetable intake revealed no associations between any of the individual carotenoids and polyp prevalence or between total carotenoids and polyp prevalence.

Adenomatous Polyps↗

A solitary Peutz-Jeghers-type hamartomatous polyp of the rectum: report of a case and review of the literature.

A solitary Peutz-Jeghers-type polyp of the rectum in a 64-year-old Japanese man is reported. Barium enema and endoscopic examination revealed a solitary polypoid lesion in the rectum. The polyp was pedunculated, and measured 2 x 1.5 x 1.5 cm. The patient had neither mucocutaneous pigmentation nor a family history of gastro-intestinal polyposis. Histopathologically, this polyp had an arborizing muscular network originating from the muscularis mucosa, and was covered by well organized mucosa with epithelial hyperplasia. The smooth muscle bundles in the polyp were thicker than those seen in Peutz-Jeghers syndrome, but their network was not as complex.

Hamartoma↗

Elastic tissue in fibroepithelial polyps.

Fibroepithelial polyps are common cutaneous lesions with an unknown etiology. We attempted to demonstrate that fibroepithelial polyps develop secondary to a focal loss of elastic tissue. Forty-five fibroepithelial polyps were examined. All were stained with Verhoeff-van Gieson stain for elastic tissue and examined. All but one specimen had a normal amount of elastin and none revealed abnormally shaped elastic fibers. Abnormal or decreased elastic tissue is not the cause of fibroepithelial polyps.

Elastic Tissue↗

Fibroepithelial polyps of the anus: a histologic, immunohistochemical, and ultrastructural study, including comparison with the normal anal subepithelial layer.

Fibroepithelial polyps of the anus (FEPA) are relatively common lesions that have attracted little attention. A series of 40 FEPA, together with sections from normal anal mucosa, were studied histologically, histochemically, immunohistochemically, and ultrastructurally. The polyps consisted of myxoid or collagenous stroma covered by squamous epithelium. Stromal cells with two or more nuclei were found in 30 polyps (80%). In five cases (12%) these cells showed atypical nuclear features. All the polyps harboring atypical cells were of large size. Mast cells were frequently present and sometimes intimately related to the stromal cells. Stromal cells stained positive for vimentin and negative for actin. Desmin was expressed in 30% of the cases. Electron microscopic examination confirmed the fibroblastic and myofibroblastic nature of the stromal cells. Examination of the subepithelial connective tissue from the normal anal mucosa showed bizarre multinucleated cells and mast cell infiltration. It is concluded that FEPA are benign lesions characterized by the presence of mononucleated and multinucleated, sometimes atypical stromal cells showing fibroblastic and myofibroblastic differentiation. The morphologic similarity between FEPA and normal anal mucosa supports the hypothesis that FEPA may represent a reactive hyperplasia of the subepithelial connective tissue of the anal mucosa. Mast cells, by means of their fibrogenic, fibrolytic, and angiogenic activities may play an important role in the pathogenesis of FEPA.

Adolescent↗

Cellular pseudosarcomatous fibroepithelial stromal polyps of the lower female genital tract: an underrecognized lesion often misdiagnosed as sarcoma.

Fibroepithelial stromal polyps of the vulvovaginal region are benign lesions that, when bland or hypocellular, are readily recognized. However those that exhibit bizarre cytomorphology, atypical mitoses, or hypercellularity, raising the possibility of malignancy, continue to be underrecognized. The authors reviewed a series of fibroepithelial stromal polyps to characterize further the morphologic features that can lead to a misdiagnosis of sarcoma. A total of 33 of 65 consecutive cases of fibroepithelial stromal polyps retrieved from the authors' consultation files were remarkable for marked hypercellularity (33 of 33), marked cytologic pleomorphism (21 of 33), mitotic counts of more than 10 mitoses per 10 high-power fields (12 of 33), and the presence of atypical mitoses (14 of 33). A total of 16 of 33 lesions had three or more of these features. Important morphologic clues to the diagnosis (shared with usual polyps at this site) were lack of an identifiable lesional margin, extension of abnormal stromal tissue up to the mucosal-submucosal interface, and the frequent presence of individually scattered multinucleate stromal cells, most often located close to the surface epithelium. Immunohistochemically, seven of 12 cases were desmin positive and one of 11 cases were smooth muscle actin positive. The age range of patients was 16 to 75 years (median, 32 years), and 21 patients (64%) were premenopausal. Sites included the vagina (18 of 33), cervix (seven of 33), and vulva (eight of 33). A total of 14 of 33 patients were pregnant, three patients were taking Tamoxifen, and one patient was on oral progesterone. Eight of 33 patients had multiple lesions at the time of presentation, of whom five were pregnant. Clinical follow-up was available in 21 of 33 patients. Three of 21 patients with follow-up had local, nondestructive recurrence. Two of these patients had multiple recurrences. None of the patients followed developed metastases. Cytologic atypia has been a previously recognized feature in these lesions; however, the occurrence of marked stromal cellularity and a mitotic rate of more than 10 mitoses per 10 high-power fields have not been emphasized previously. Moreover, the combination of these features has only rarely been documented. Awareness of the spectrum of histologic features that these lesions can exhibit is crucial in their accurate recognition, thus avoiding potential overtreatment.

Adolescent↗

Colonoscopy and the management of polyps containing invasive carcinoma.

Experiences with 565 colonoscopic polypectomies and 91 colonic and rectal resections containing infiltrating carcinoma in polyps are reviewed. A plan of management based on pathologic study of resected polyps is formulated to avoid further unnecessary surgery. It was concluded that: (1) Tubular adenomas containing invasive carcinomas have a low incidence of metastatic node involvement. This incidence is related to the depth of carcinomatous involvement. Resection of these polyps with a margin free of carcinoma constitutes definitive and adequate treatment and that (2) Villous adenomas containing invasive carcinoma have a high incidence of metastatic nodal involvement, and operative resection of the involved area of the colon is recommended, and that (3) Pedunculated tubulovillous adenomas containing invasive carcinoma behave like tubular adenomas, and the recommendations for further surgery in the patient with tubular adenomas with carcinoma apply equally well for these lesions. Sessile tubulovillous polyps tend to behave like villous adenomas, and if invasive carcinoma is demonstrated, further operation is recommended.

Adenoma↗