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Biomedical subjects

M Z Gilcrease

Publications and source records attributed to M Z Gilcrease.

At least 19 recordsLinked to original sources

Expression of protease-activated receptor 1 in oral squamous cell carcinoma.

Protease-activated receptor 1 (PAR-1) is a G-coupled membrane protein. In this study, we analyzed the expression of PAR-1 in oral squamous cell carcinomas (SCCs). PAR-1 was expressed in oral SCCs, but the level of PAR-1 protein was lower in non-metastatic cells than in metastatic cells. Thrombin stimulated the growth of metastatic cells, and both thrombin and thrombin receptor activation peptide (TRP) enhanced the adhesion of these cells to fibronectin, but had no effect on non-metastatic cells. Thrombin and TRP also induced matrix metalloproteinase (MMP)-2 and MMP-9 activities in metastatic cells. These results suggest that PAR-1 may contribute to the growth and invasive potential of oral SCC.

Blotting, Western↗

Adhesion of aspirated tumor cells to extracellular matrix proteins: a new methodology utilizing fine-needle aspiration.

BACKGROUND: Cell adhesion molecules mediate the interactions of cells with other cells and with extracellular matrix components. Such interactions may be important in the development of tumor invasion and metastasis. This article describes a new approach to the evaluation of tumor cell-matrix interactions by utilizing fine-needle aspiration of resected tumors. METHODS: Fine-needle aspiration was performed on 15 fresh surgical specimens of various types of carcinomas. After partial purification by isotonic Percoll centrifugation, tumor cell adhesion to collagen Type IV, laminin, and fibronectin was evaluated by counting cytologically malignant cells adhering to matrix-coated plastic substrates. Frozen tissue sections of the corresponding tumors were studied simultaneously for immunohistochemical expression of alpha-2, alpha-3, alpha-4, and alpha-5 integrin subunit expression. Results of the immunohistochemical staining then were compared with the adhesion data for particular tumors. RESULTS: In general, the majority of the tumors exhibited little or no adhesion to collagen or laminin, but several tumors showed marked adhesion to fibronectin. Striking differences were noted between some tumors of the same histologic subtype. Competitive inhibition studies performed with two of the tumors (a large cell carcinoma and a renal cell carcinoma) showed decreased adhesion to fibronectin in the presence of anti-alpha-5, suggesting at least a partial role for the alpha-5-beta 1 fibronectin receptor in mediating the adhesion of these tumors to fibronectin. All the tumors examined exhibited strong immunohistochemical expression of the alpha-2 and alpha-3 integrin subunits, and all were negative for alpha-4. Three of the tumors showed weak expression of alpha-5, two of which (a squamous cell carcinoma and a renal cell carcinoma) were the tumors that showed the greatest adhesion to fibronectin. CONCLUSIONS: Quantitative adhesion data can be obtained using cell suspensions prepared from fine-needle aspirates, and there are marked differences in adhesive properties between particular tumors. Although two of the tumors showed a correlation between adhesion to fibronectin and immunohistochemical expression of the alpha-5 integrin subunit, matrix adhesion does not necessarily correlate with immunohistochemical expression of adhesion molecule receptors. In the future, this methodology potentially could be of value in determining which patients may benefit from therapies aimed at modifying tumor cell-matrix interactions.

Biopsy, Needle↗

Correlation of CD44S expression in renal clear cell carcinomas with subsequent tumor progression or recurrence.

BACKGROUND: Recent reports have shown altered expression of CD44 in renal cell carcinomas. However, to the authors' knowledge there are no data correlating CD44 expression in renal cell carcinomas with subsequent tumor progression or recurrence, nor is there information about the presence of particular splice variants of CD44 in these tumors. METHODS: The authors examined the immunohistochemical expression of CD44S, the standard isoform of CD44, in renal cell carcinomas from 43 patients using 2 different monoclonal antibodies, Mab2137 and Hermes-3. In addition, they stained the renal cell carcinomas with antibodies to 2 splice variants of CD44, CD44v3 and CD44v6. RESULTS: Increased staining of renal clear cell carcinomas with Mab2137 was observed in high grade versus low grade tumors (45% vs. 0%, P = 0.013), whereas increased staining of clear cell carcinomas with Hermes-3 was noted in high stage versus low stage tumors (40% vs. 0%, P = 0.006). Few tumors stained with antibodies to CD44v3. Although increased expression of the splice variant CD44v6 was noted in papillary versus clear cell carcinomas, and increased staining of papillary carcinomas with Mab2137 and with antibodies to CD44v6 was noted for low stage versus high stage tumors, these differences did not achieve statistical significance. Clinical follow-up of at least 43 months was available for 26 patients. Six of these patients (five with clear cell carcinoma and one with papillary carcinoma) developed progressive or recurrent disease. The primary tumors from all 5 patients with progressive or recurrent clear cell carcinoma showed staining with Mab2137, whereas the primary tumors from only 2 of the 15 patients with at least 43 months follow-up and no evidence of progressive or recurrent clear cell carcinoma (13%) showed staining with Mab2137 (P = 0.001). Alternatively, 5 of 7 clear cell carcinomas (71%) that stained with Mab2137 were from patients who subsequently developed recurrence or progression, compared with 0 of 13 clear cell carcinomas that did not stain. Similar findings were not observed for papillary carcinomas, which appeared to be biologically distinct from clear cell carcinomas. CONCLUSIONS: CD44S staining with Mab2137 correlates with progression or recurrence of clear cell renal cell carcinoma. CD44S may, therefore, play a pathogenetic role in tumor progression.

Adult↗

Extra-articular synovial chondromatosis of the temporomandibular joint: pitfalls in diagnosis.

Synovial chondromatosis is a benign disease that only rarely affects the temporomandibular joint. When it does, disease is usually confined to the joint space itself but can occasionally extend beyond the joint capsule into the parotid gland, temporal bone, or cranium. The local clinical behavior, radiographic appearance, and histopathologic features can combine to create the appearance of a malignant lesion. We report a case of synovial chondromatosis that affected the temporomandibular joint and presented as an external auditory canal mass. The lesion was thought to be a chondrosarcoma prior to the definitive resection. Pitfalls in the diagnosis and management of synovial chondromatosis are discussed.

Chondromatosis, Synovial↗

Intrasellar adenoid cystic carcinoma and papillary mucinous adenocarcinoma: two previously undescribed primary neoplasms at this site.

Most carcinomas involving the sella turcica are metastases. We report two previously undescribed carcinomas that appear to be primary at this site. The first occurred in a 44-year-old woman who presented with hemianopsia. A mass was noted by computed tomography to occupy the sella turcica, from which it appeared to originate. Transphenoidal biopsy showed the tumor to be an adenoid cystic carcinoma with a typical cribriform pattern. The patient died shortly after a subsequent attempt at tumor resection. The second tumor arose in a 55-year-old man who presented with diplopia. Computed tomography showed a mass in the sella turcica that was presumed to be a pituitary adenoma. However, transphenoidal resection revealed a mucinous adenocarcinoma composed of small papillae and glands lined by columnar epithelium. The tumor cells exhibited varying degrees of stratification with prominent interspersed mucin vacuoles. Focal solid areas showed a component of signet ring-type cells. In contrast to the apparent aggressive behavior of the adenoid cystic carcinoma, the papillary mucinous adenocarcinoma appeared much less aggressive, as the second patient was alive and without evidence of disease 5 years later. Both tumors may be derived from epithelial rests within the pituitary gland, either minor salivary gland rests or Rathke's cleft remnants.

Adenocarcinoma, Mucinous↗

Fine-needle aspiration of basaloid squamous carcinoma: a case report with review of differential diagnostic considerations.

Basaloid squamous carcinoma is a distinct variant of squamous carcinoma with a particularly poor prognosis. To our knowledge, there are only two papers in the cytopathology literature which describe this entity. We report the fine-needle aspiration findings of an additional case of metastatic basaloid squamous carcinoma in a cervical lymph node and compare its cytomorphologic features to those observed on touch imprints of the subsequent surgical specimen. Smears of the aspirate showed a mixed lymphoid background with interspersed cohesive clusters of small cells roughly 3 times the size of small mature lymphocytes. Some cells were angulated and others exhibited irregular nuclear contours. The cells were generally hyperchromatic with evenly staining dense chromatin or irregularly distributed coarse chromatin. Focally there was evidence of nuclear molding. On Diff-Quik staining, irregular globules of magenta-stained extracellular dense material were noted within or adherent to the periphery of some clusters or as somewhat linear formations with small epithelial cells clinging to the edges. Abundant mitotic figures and clumps of necrotic tumor were more apparent on touch preps of the subsequent surgical specimen. The differential diagnosis by fine-needle aspiration includes adenoid cystic carcinoma, basal-cell adenocarcinoma, adenosquamous carcinoma, and small-cell carcinoma. If a fine-needle aspirate of a cervical lymph node shows the features described above and the primary tumor is unknown, suggesting the possibility of metastatic basaloid squamous carcinoma may aid clinicians in the search for a primary site, as basaloid squamous carcinoma occurs most frequently at the base of the tongue, hypopharynx, and supraglottic larynx.

Adenocarcinoma↗

Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: a histopathologic and immunohistochemical comparison.

Because of histological similarities between nephrogenic adenomas and clear cell adenocarcinomas of the urinary tract, there is the potential for diagnostic confusion between these two entities. The histopathologic features of 13 nephrogenic adenomas and five clear cell adenocarcinomas of the urethra and urinary bladder are compared in this report, and detailed immunohistochemical staining profiles are provided for these tumors. Only 2 of the 13 nephrogenic adenomas contained clear cells, and these constituted less than 10% of the lesions. In contrast, four of the five clear cell adenocarcinomas contained prominent areas with clear cells. Nephrogenic adenomas generally showed only mild cytologic atypia, whereas four of the five clear cell adenocarcinomas showed severe atypia. A single mitotic figure was identified in only two of the nephrogenic adenomas, whereas the mitotic rate in the clear cell adenocarcinomas ranged from 2 to 14 per 10 high-power fields. None of the nephrogenic adenomas showed evidence of necrosis, but focal necrosis was noted in four of the five clear cell adenocarcinomas. In general, the nephrogenic adenomas and clear cell adenocarcinomas showed negative to weak staining with CK903 but strong staining with AE1, AE3, and Cam 5.2. Variable staining was observed with Brst-3 and antibodies to S-100, CEA (monoclonal and polyclonal), LeuM-1, and CA19.9. Nephrogenic adenomas and clear cell adenocarcinomas were all negative for prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and estrogen and progesterone receptors (except for two nephrogenic adenomas, which showed only focal weak staining for estrogen receptor). Neither bcl-2 nor c-erbB-2 staining was able to discriminate between the tumors. However, strong staining for p53 was noted in each clear cell adenocarcinoma and in none of the nephrogenic adenomas. MIB-1 positivity in nephrogenic adenomas ranged from 0 to 13 (average of 5.5) per 200 cells, whereas the positive range for clear cell adenocarcinomas was 33 to 70 (average of 47) per 200 cells. In summary, histopathologic features that favor clear cell adenocarcinoma over nephrogenic adenoma include a predominance of clear cells, severe cytological atypia, high mitotic rate, necrosis, high MIB-1 positivity, and strong staining for p53.

Adenocarcinoma, Clear Cell↗

Tyrosine-rich crystals associated with oncocytic salivary gland neoplasms.

OBJECTIVE: Crystalloids have been identified ultrastructurally within the epithelial cells of Warthin's tumors, but there have been no studies characterizing crystals or crystalloids in Warthin's tumors by light microscopy. The finding of abundant needle-shaped crystals in a fine-needle aspirate of a cystadenoma of the parotid prompted us to examine the prevalence of crystals and crystalloids in oncocytic salivary gland neoplasms. DESIGN: Ninety-seven oncocytic neoplasms (93 Warthin's tumors, 3 cystadenomas, and 1 oncocytoma) excised at our institution between 1950 and 1996 were examined, to identify crystals. Neoplasms with crystals were further characterized by means of a variety of histochemical stains and electron microscopy. Ninety-nine pleomorphic adenomas were similarly reviewed. RESULTS: Seven cases with crystals were identified. Five of these were Warthin's tumors, 1 was a cystadenoma, and 1 was an oncocytoma. The crystals were noted within tumor cysts but were not limited to the neoplasms. The crystals were predominantly either needle-shaped or tabular, but some cases contained mixtures of both as well as intermediate forms. They stained pink with hematoxylin-eosin, although the tabular forms also exhibited a focal yellow hue. The crystals were not discernible under polarized light. They stained a red-brown color with Millon's reagent, which indicated the presence of tyrosine. Trichrome, periodic acid-Schiff stain with diastase, alcian blue (pH 2.5), and Congo red stains were negative. Electron microscopy revealed sharply defined, elongate, electron-dense structures with periodicity, both extracellular and within epithelial cells. No crystals or crystalloids were identified in any of 99 pleomorphic adenomas reviewed. CONCLUSIONS: The findings indicate that tyrosine-rich crystals associated with several oncocytic salivary gland neoplasms are morphologically, histochemically, and ultrastructurally distinct from previously described tyrosine-rich crystalloids and collagenous crystalloids of pleomorphic adenomas. Although the crystals appear to form by the assembly of small units within epithelial cells, the exact mode of formation remains unclear.

Adenolymphoma↗

Testicular Sertoli cell tumor with a heterologous sarcomatous component: immunohistochemical assessment of Sertoli cell differentiation.

OBJECTIVE: Immunohistochemical staining is reported to be useful in distinguishing ovarian Sertoli-stromal cell tumors from carcinosarcomas. To assess Sertoli cell differentiation in a rare malignant biphasic testicular tumor, we compared the immunophenotypic profile of the tumor with that of Sertoli cell nodules and adenomas and mullerian carcinosarcomas. DESIGN: Immunohistochemical staining was performed on 6 testes (4 with hyperplastic Sertoli cell nodules, 2 with Sertoli cell adenomas) and 7 carcinosarcomas (6 involving the uterus, 1 involving the uterus and ovary) using primary monoclonal antibodies AE1/AE3, CAM 5.2, CA 19.9, and antibodies directed against epithelial membrane antigen, carcinoembryonic antigen (monoclonal and polyclonal), S100, placental alkaline phosphatase, and inhibin. These staining results were compared with those of the index case. RESULTS: All testes showed positive staining for inhibin and vimentin in the Sertoli cells of the nodules and adenomas. One Sertoli cell nodule showed focal staining with AE1/AE3 and CAM 5.2. Both adenomas showed focal positive staining for S100. All nodules and adenomas were negative for epithelial membrane antigen, monoclonal and polyclonal carcinoembryonic antigen, CA 19.9, and placental alkaline phosphatase. In contrast, the carcinomatous areas of the carcinosarcomas were all negative for inhibin but exhibited positive staining for AE1/AE3, CAM 5.2, and epithelial membrane antigen. The carcinosarcomas showed variable expression of vimentin, S100, carcinoembryonic antigen, CA 19.9, and placental alkaline phosphatase. The epithelial component of the tumor from the index case showed strong diffuse staining for inhibin and vimentin and only very faint focal staining with AE1/AE3 and CAM 5.2. The epithelial component was negative for epithelial membrane antigen, monoclonal and polyclonal carcinoembryonic antigen, S100, CA 19.9, and placental alkaline phosphatase. CONCLUSIONS: The immunohistochemical findings in the index case support the diagnosis of Sertoli cell tumor with a heterologous sarcomatous component over carcinosarcoma. Inhibin seems to be the best single marker for Sertoli cell differentiation. To our knowledge, only 1 other case of this rare testicular tumor has been reported in the literature.

Aged↗

Localized thymic Langerhans' cell histiocytosis and its relationship with myasthenia gravis. Immunohistochemical, ultrastructural, and cytometric studies.

OBJECTIVE: It has been suggested that localized Langerhans cell histiocytosis may represent an exaggerated form of a proliferative process that has been reported in a few patients with myasthenia gravis. To evaluate the relationship between thymic Langerhans' cell proliferation and myasthenia gravis, we analyzed a rare case of localized thymic Langerhans' cell histiocytosis and examined thymic Langerhans' cell distribution in myasthenic and control patients. DESIGN: Immunohistochemical, ultrastructural, and image cytometric DNA analyses were performed on the index case. Immunostaining for S100 was performed on 20 additional thymuses, 10 from patients with myasthenia gravis and 10 from control patients. RESULTS: Immunohistochemical studies revealed no increase in Langerhans' cells in the surrounding thymic tissue of the index case. No difference was found between the number of Langerhans' cells in the remaining thymuses of myasthenia patients compared with the control group, and no micronodular proliferations were identified in either group. CONCLUSIONS: Localized thymic Langerhans' cell histiocytosis is an unusual lesion that is associated with myasthenia gravis in some patients. In the few cases reported at present, however, the lesion does not appear to be related pathogenetically to myasthenia gravis.

Adult↗

Correlation of very late activation integrin and CD44 expression with extrarenal invasion and metastasis of renal cell carcinomas.

Cell adhesion molecules mediate cell-cell and cell-matrix interactions, and they are thought to play an important role in tumor invasion and metastasis. Altered expression of integrins and CD44 in renal cell carcinoma has been recently demonstrated, but an association with invasive or metastatic behavior has not been reported. We examined very late activation (VLA) integrin and CD44 expression in 37 renal cell carcinomas and correlated adhesion molecule expression with multiple histological and clinical parameters. Most tumors exhibited positive staining for VLA3 (81%). Approximately one third of the tumors stained positively for VLA6 and CD44, and fewer (27%) were positive for VLA2. Only a few tumors were positive for VLA4 (8%) and VLA5 (14%). Most of the tumors exhibiting positive staining showed a combination of membranous and cytoplasmic staining patterns. Low-grade tumors positive for VLA6 showed a tendency for basilar staining of the tumor cells, whereas high-grade tumors exhibited diffuse cytoplasmic staining. All tumors exhibiting weak or strong positive staining for VLA4 or VLA5 showed extrarenal invasion or were known to have developed metastases at the time of nephrectomy. All tumors strongly positive for VLA2 or CD44 showed invasion beyond the renal capsule or metastases. In contrast to a previous study, no association was observed between positive staining and tumor grade. Nor were tumor size, architectural pattern, cell type, or DNA ploidy found to be associated with particular staining patterns. Although many of the invasive tumors showed no difference in VLA integrin or CD44 expression compared with tumors confined to the kidney, increased expression in some of them suggests that these cell adhesion molecules may contribute to the invasive or metastatic phenotype.

Carcinoma, Renal Cell↗

Yolk sac tumor identified at autopsy after surgical excision of immature sacrococcygeal teratoma.

Although the predictive value of immature elements in sacrococcygeal teratomas in unclear, there are reports of malignant recurrence after surgical resection of immature sacrococcygeal teratomas. The recurrent tumors are presumed to arise from small residual malignant foci not identified at the time of surgical resection. In this report a premature female infant was delivered at 29 week's gestation with a large sacrococcygeal teratoma. The tumor weighed 1,350 g. It was largely cystic with a focal nodular and variegated appearance. Histologically, the tumor was a grade 1 immature teratoma with a predominance of neuroglial elements. No malignant elements were identified in any of 26 sections examined. The infant died intraoperatively of cardiovascular complications related to the large vascular supply of the tumor but had a grossly complete resection of tumor. At autopsy, a small microscopic focus of yolk sac tumor was identified adjacent to the sacrum anteriorly. Had the infant survived, this focus might well have been a source for malignant recurrence.

Autopsy↗

Somatic von Hippel-Lindau mutation in clear cell papillary cystadenoma of the epididymis.

Papillary cystadenoma of the epididymis is an uncommon benign lesion that may occur sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. Neither immunohistochemical studies nor molecular genetic analyses of the VHL gene have been reported previously for this lesion. The authors describe two cases of clear cell papillary cystadenoma of the epididymis, both of which were initially confused with metastatic renal cell carcinoma. Both lesions showed positive immunohistochemical staining for low and intermediate molecular weight keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, alpha 1-antitrypsin, and alpha 1-antichymotrypsin. Each was negative for CEA. Because clear cell papillary cystadenoma is similar to renal cell carcinoma histologically, and because both occur as components of the von Hippel-Lindau disease complex, the authors analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL gene mutation was detected in one of the two tumors by polymerase chain reaction followed by single-strand conformation polymorphism analysis. Direct sequencing revealed a cytosine to thymine transition at nucleotide 694, resulting in the replacement of an arginine with a stop codon after the sixth amino acid of exon 3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene mutations may play a role in the initiation of tumorigenesis in sporadic cystadenomas of the epididymis.

Adenocarcinoma, Clear Cell↗

Human monocyte interactions with non-enzymatically glycated collagen.

We have previously shown that receptors for advanced glycation end products are expressed on activated human monocytes. We now report that activated human monocytes exhibit increased adhesion to non-enzymatically glycated collagen substrates (+32% +/- 1, p less than 0.001), and the increased adhesion can be competitively inhibited with non-enzymatically glycated albumin. Non-activated monocytes, which do not express receptors for advanced glycation end products, exhibit decreased adhesion (-16% +/- 1, p less than 0.001). Similar results were observed with substrates of fibronectin and endothelial cell matrix proteins. As the presence of glycation adducts on collagen interferes with the normal binding of monocytes/macrophages, one possible role for advanced glycation adduct receptors on activated monocytes is to counterbalance such decreased adherence. Overcompensation for long periods of time may lead to pathological changes. Additionally, such receptors may play a role in monocyte-mediated remodelling of glycated matrix proteins, as we have observed increased degradation of non-enzymatically glycated collagen substrates by activated human monocytes at 2 h (+52% +/- 11, p = 0.01), 3 h (+49% +/- 10, 10, p = 0.01), and 4 h (+36% +/- 6, p less than 0.01) after adding activated monocytes to 125I-labelled substrates.

Animals↗

Secretion of a chemotactic substance(s) by AGE-stimulated human monocytes.

Receptors for products of non-enzymatic glycosylation have been identified previously on activated human monocytes. In this study we have found that medium conditioned by activated human monocytes following stimulation with AGE-BSA elicited an almost 3-fold greater chemotactic response from other activated monocytes than conditioned medium obtained following stimulation with control BSA (44 +/- 13 and 16 +/- 4.6, respectively; n = 9, P less than 0.05). The response elicited from AGE-BSA alone was not statistically significant. It appears that stimulation of the cells via the AGE-receptor results in the secretion of increased levels of a chemotactic substance(s) for monocytes/macrophages. This mechanism may help to explain the pathogenesis of atherosclerosis in diabetes, as monocyte accumulation within the vessel wall is an important step in fatty streak development.

Chemotactic Factors↗

Neutrophil adhesion to endothelium following hyperosmolar insult.

This study examined the effects of hyperglycemic/hyperosmolar conditions on neutrophil adhesion to endothelium. A 2.4-fold increase in neutrophil adhesion was observed following exposure of endothelial cells to 100 mM glucose for 24 hours (n = 9, p less than 0.001), and a 57% increase occurred following pre-incubation in 50 mM glucose for 24 hours (n = 8, p less than 0.01). Phase-contrast microscopy of endothelial monolayers following exposure to 100 mM glucose showed no gross morphological changes, and no differences in membrane permeability were detected. Electron microscopy, however, revealed that cells exposed to 100 mM glucose generally had more pseudopods, an increased density of cytoplasm, and more finely dispersed chromatin throughout the nucleus. Increased neutrophil adhesion to endothelium was also observed following exposure of endothelial cells to 100 mM mannitol, indicating that hyperosmolarity could account for the effect observed with high concentrations of glucose. However, the increase following mannitol treatment was 170% of control (n = 6), while glucose pre-treatment resulted in a 240% increase (n = 9, p = 0.01 for glucose compared to mannitol). The effect of high concentrations of glucose on neutrophil adhesion to endothelial cells was to some degree specific for endothelium, as the same effect was not observed with microvascular pericytes. As neutrophil adhesion to endothelium is an important early step in the acute inflammatory response, these findings may help to explain the increased incidence and severity of infections in diabetic patients.

Animals↗