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Gregory T MacLennan

Publications and source records attributed to Gregory T MacLennan.

At least 19 recordsLinked to original sources
PubMed2006

Alpha-methylacyl-CoA racemase (P504S)/34betaE12/p63 triple cocktail stain in prostatic adenocarcinoma after hormonal therapy.

Alpha-methylacyl-CoA racemase (AMACR) has recently been shown to be a highly sensitive marker for the diagnosis of prostate cancer. However, there is limited information concerning its utility as a marker for prostate carcinoma after hormonal therapy. Our current investigation was conducted to evaluate the expression of AMACR in patients with prostate carcinoma after hormonal therapy and assess its diagnostic utility in combination with p63 and high molecular weight cytokeratin (34betaE12) staining. Prostate tissues from 49 patients who had been treated with hormonal therapy were immunohistochemically analyzed for AMACR, 34betaE12, and p63 expression by a triple antibody cocktail stain. The staining intensities and the percentages of positively staining tumor cells were recorded. The correlations between AMACR expression and metastatic status, associated hormonal therapy regimens, and the extent of hormone therapy effect were analyzed. All malignant acini were completely negative for both basal cell markers (34betaE12 and p63). Tumor cells failed to demonstrate expression of AMACR in 14 (29%) of 49 cases. In the remaining 35 cases (71%), positive immunostaining for AMACR was noted, but with variable intensities and percentages of cells stained. Positive staining for AMACR in benign glands was not seen in any case. In all cases, basal cells were strongly stained by p63 in benign acini with a mean positive percentage of 96%. Similarly, basal cells in benign acini displayed moderate staining intensities for 34betaE12 in 3 (7%) of 41 cases and strong immunostaining for this marker in the remaining 38 cases (93%); the mean percentage of positive cells was 92%. alpha-methylacyl-CoA racemase expression may be substantially diminished or entirely lost in prostate carcinoma after hormonal therapy. This variation in AMACR expression does not correlate with the metastatic status, the modality of hormonal therapy, or the extent of therapy-related effect. It is important that pathologists be aware that some hormonally treated prostate carcinomas do not express AMACR, and that immunostaining in such cases must be interpreted with caution. A triple cocktail stain using AMACR, 34betaE12, and p63 can be helpful in evaluating prostate specimens for the presence of residual or recurrent carcinoma after hormonal therapy for cancer.

Adenocarcinoma↗
PubMed2006

Histologic grading of noninvasive papillary urothelial neoplasms.

OBJECTIVES: In 1998, a revised system of classifying noninvasive papillary urothelial neoplasms of the urinary bladder was proposed and subsequently formally adopted by the World Health Organization (WHO). The introduction of this new system was justified as being potentially superior on a number of levels to the 1973 WHO classification system that it replaced. Specifically, a new category of neoplasms, designated papillary urothelial neoplasm of low malignant potential (PUNLMP), was considered advantageous for several reasons. The new system was expected to gain widespread acceptance, improve reproducibility of diagnoses among pathologists, and enhance the correlation between urine cytology and tumor histology. We examine the history of the changes in terminology for these lesions, the relative merits of PUNLMP terminology, the extent to which the expectations accompanying the new grading system have been met, and the extent to which the new system has enhanced the management of patients with noninvasive papillary urothelial neoplasms of the bladder. METHODS: A PubMed literature search after the introduction of this new classification was performed and relevant papers reviewed. RESULTS AND CONCLUSIONS: The 2004 WHO classification is a positive initiative in attempting to standardize urothelial tumor grading by expanding and clearly defining the morphologic characteristics of noninvasive papillary urothelial neoplasms. The new terminology used in this system is of questionable validity and utility. Full-genome searches for prognostic and predictive molecular gene expression signatures, GeneChip technology and proteomics techniques, and several new biomarkers and molecular tests may be useful in future grading schemes after their clinical utility is better established.

Carcinoma, Transitional Cell↗
PubMed2006

Interphase fluorescence in situ hybridization analysis of chromosome 12p abnormalities is useful for distinguishing epidermoid cysts of the testis from pure mature teratoma.

PURPOSE: The distinction of epidermoid cyst of the testis from teratoma is of critical importance because the former is benign and the latter is a malignant tumor that may have associated metastasis of either teratomatous or non-teratomatous germ cell tumor types. Chromosome 12p abnormalities are seen in the vast majority of testicular germ cell tumors of adults and are present in all histologic subtypes. In this study, we investigated the clinical utility of interphase fluorescence in situ hybridization (FISH) analysis of chromosome 12p abnormalities for distinguishing epidermoid cysts of the testis from pure mature teratoma. EXPERIMENTAL DESIGN: Sixteen testicular epidermoid cysts and 17 testicular teratomas were investigated for isochromosome 12p [i(12p)] and 12p overrepresentation using interphase FISH analysis. RESULTS: Neither i(12p) nor 12p overrepresentation were observed in 16 epidermoid cyst cases, whereas i(12p) was detected in 76% of teratomas and 12p overrepresentation was identified in 29% of teratomas. Overall, 88% of testicular teratomas had chromosome 12p abnormalities. CONCLUSIONS: FISH identification of i(12p) and/or 12p overrepresentation in routinely processed surgical specimens is a useful ancillary diagnostic tool in distinguishing testicular epidermoid cysts from teratoma.

Adolescent↗
PubMed2006

Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder.

Intestinal metaplasia has been proposed to be a precursor lesion of adenocarcinoma in the urinary bladder. CDX2 is a transcription factor that is encoded by a homeotype gene that plays an essential role in the differentiation and proliferation of intestinal epithelial cells. Hepatocyte-specific antigen (Hep) has also been shown to be a useful marker of intestinal metaplasia. Tissues from 46 patients, including 22 cases of intestinal metaplasia of the urinary bladder, 11 cases of typical cystitis glandularis, and 13 cases containing both lesions, were selected and immunohistochemical stains for CDX2, Hep, cytokeratin 20 (CK20), and cytokeratin 7 (CK7) were performed. Nuclear staining for CDX2 was observed in 29 of 35 (83%) cases of intestinal metaplasia of the urinary bladder. In contrast, nuclear staining for CDX2 was not observed in any case of typical cystitis glandularis; however, seven of 24 (29%) cases showed aberrant cytoplasmic expression in a mean of 37% of cells. CK20 was expressed in 28 of 35 (80%) cases of intestinal metaplasia, but was observed in only one of 24 (4%) cases of cystitis glandularis in 15% of cells. CK7 was expressed in only six of 35 (17%) cases of intestinal metaplasia, whereas expression of CK7 was observed in all cases (100%) of typical cystitis glandularis with a mean percentage of positively staining cells of 63%. The mean percentages of positively staining cells in intestinal metaplasia with CDX2, CK20, and CK7 were 55, 49, and 53%, respectively. All examples of both intestinal metaplasia and typical cystitis glandularis were uniformly negative for Hep. In the urinary bladder, intestinal metaplasia and typical cystitis glandularis have sharply contrasting immunoprofiles. Additionally, the absence of Hep staining in intestinal metaplasia of the urinary bladder, despite its morphologic resemblance to normal colonic mucosa and intestinal metaplasia in other organs, may signify the presence of unique metaplastic pathways in the urinary bladder.

Autoantigens↗
PubMed2006

Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis.

It is hypothesized that oxalate plays an active role in calcium oxalate (CaOx) nephrocalcinosis and oxalate driven nephrolithiasis by interacting with the kidney. We developed an adjustable, nonprecursor, continuous infusion model of hyperoxaluria and CaOx nephrocalcinosis to investigate this hypothesis. Minipumps containing PBS or KOx (60-360 micromol/day; n = 5-7/dose) were implanted subcutaneously in male Sprague-Dawley rats on D0 and D6. Rats were killed on D13. Oxalate excretion and CaOx crystalluria were monitored by 20+4 h urine collections. Localization and content of intrarenal crystals were determined on frozen sections using polarization and microFTIR. Oxalate excretion was significantly elevated in all KOx rats (P < or = 0.005). CaOx crystalluria was most persistent in the 240-360 micromol/day KOx rats, but even 60 micromol/day KOx rats showed sporadic crystalluria. One hundred percent of KOx rats had CaOx nephrocalcinosis as confirmed by microFTIR. Most crystals were localized to the lumens of the corticomedullary collecting ducts. A few crystals are localized just under the papillar urothelium. The minipump model is the first model of hyperoxaluria to provide continuous infusion of oxalate. It permits control of the levels of hyperoxaluria, crystalluria and CaOx nephrocalcinosis. The level of sustained hyperoxaluria and CaOx nephrocalcinosis induced by treatment with 360 micromol/day KOx for 13D models the conditions frequently observed in jejunoileal bypass patients. Adjustments in the length of treatment and level of hyperoxaluria may allow this model to also be used to study the oxalate driven CaOx-nephrolithiasis common in patients with hyperoxaluria due to other causes.

Animals↗
PubMed2006

Gonadoblastoma.

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Gonadoblastoma↗
PubMed2006

The influence of chronic inflammation in prostatic carcinogenesis: a 5-year followup study.

PURPOSE: We investigated an association between chronic prostatic inflammation and prostate carcinogenesis. MATERIALS AND METHODS: Initial prostate needle biopsies from 177 patients with clinical parameters suspicious for malignancy were examined. We evaluated them for the presence and extent of chronic inflammation and other pathological findings. Findings in followup biopsies during the next 5 years were reviewed and correlated with the initial results. RESULTS: Two patients subset were identified, including 144 patients with and 33 without chronic inflammation in the initial biopsies. Additional pathological findings in some cases in each group included simple atrophy, high grade prostatic intraepithelial neoplasia, adenocarcinoma and atypical small acinar proliferation. Post-atrophic hyperplasia and proliferative inflammatory atrophy were noted only in patients with chronic inflammation. A significant association between serum prostate specific antigen and the degree of inflammation was observed in needle biopsies. In repeat biopsies within 5 years in patients with chronic inflammation 29 new cancers were diagnosed, representing a new cancer incidence of 20%. Of these cancers 6 occurred in patients in whom initial biopsies showed only chronic inflammation, 15 occurred in patients with initial post-atrophic hyperplasia/proliferative inflammatory atrophy lesions, 7 occurred in patients with initial high grade prostatic intraepithelial neoplasia and chronic inflammation, and 1 occurred in a patient with initial atypical small acinar proliferation and chronic inflammation. High grade prostatic intraepithelial neoplasia was newly discovered in 9 patients in the initial chronic inflammation group, of whom 7 had post-atrophic hyperplasia/proliferative inflammatory atrophy and 2 had simple atrophy and chronic inflammation in the initial biopsies. In contrast, in 33 patients initially showing no inflammation adenocarcinoma was subsequently found in 2 (6%). One of these patients had high grade prostatic intraepithelial neoplasia and the other had atypical small acinar proliferation on initial biopsies. CONCLUSIONS: Chronic inflammation may be a significant risk factor for prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Retroperitoneal seminoma in limited biopsies: morphologic criteria and immunohistochemical findings in 30 cases.

The incidence of retroperitoneal seminoma is much less than that of its gonadal counterpart. Accurate diagnosis of retroperitoneal seminoma is critical, because it carries an excellent prognosis due to its favorable response to radiation therapy and/or cisplatin-based chemotherapy. However, correctly diagnosing a retroperitoneal seminoma may be challenging, especially when the biopsy material is limited. The present study was conducted to evaluate histologic findings and immunohistochemical staining patterns in biopsy specimens of retroperitoneal seminoma and to compare their utility as diagnostic tools. Thirty biopsy specimens of retroperitoneal seminoma were assessed for histologic characteristics and immunohistochemical expression of OCT4, c-kit, placental-like alkaline phosphatase, and cytokeratin AE1/AE3. The clinical information, morphologic features, and staining intensities and the percentages of positively staining tumor cells were analyzed. The mean age of patients was 38 years. Lymphocytic infiltration and nucleolar prominence in tumor cells were found in all 30 cases (100%). The incidence of other histologic characteristics were as follows: fibrous septa/stroma in 80% (24 cases), clear tumor cell cytoplasm in 70% (21 cases), tumor necrosis in 60% (18 cases), cellular pleomorphism in 53% (16 cases), granulomatous inflammation in 50% (15 cases), distinct cell borders in 46% (14 cases), intercellular edema in 23% (7 cases), and syncytiotrophoblasts in 3% (1 case). The mean mitotic count was 3 (range 0 to 15) per 10 high-power fields. All 30 cases (100%) of retroperitoneal seminoma revealed moderate to strong nuclear OCT4 staining in more than 50% of tumor cells. Twenty-one cases (70%) showed membranous expression of c-kit by tumor cells, with moderate to strong staining intensity in most cases. Variable degrees of staining for placental-like alkaline phosphatase were identified in 23 cases (77%) with occasional background staining artifact. Six cases (20%) displayed a positive cytokeratin AE1/AE3 staining pattern with weak to moderate intensity. In conclusion, the most common histologic findings in limited biopsy specimens of retroperitoneal seminoma were lymphocytic infiltration and nucleolar prominence in tumor cell nuclei. OCT4 immunostaining, with its superior sensitivity and easy interpretation compared with other markers, is a powerful tool for confirming the diagnosis of retroperitoneal seminoma.

Adult↗