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C B Gilks

Publications and source records attributed to C B Gilks.

At least 19 recordsLinked to original sources
PubMed1998

Papillary serous carcinoma of the uterine cervix: a clinicopathologic study of 17 cases.

The clinical and pathologic features of 17 cases of papillary serous adenocarcinoma of the cervix (PSCC) were studied in women who ranged in age from 26 to 70 years. There was a bimodal age distribution, with one peak occurring before the age of 40 years and the second peak after the age of 65. The presenting symptoms were abnormal vaginal bleeding (11 patients), abnormal exfoliative cervical cytology (four patients), or watery vaginal discharge (two patients). On pelvic examination, eight patients had a polypoid or exophytic cervical mass and two patients had an ulcerated or indurated cervix; no abnormality was detected in seven patients. Two tumors were stage Ia, 12 were stage Ib, two were stage II, and one was stage III. Nine patients were treated by radical hysterectomy and one by simple hysterectomy; six of these patients received postoperative radiotherapy. The other patients received primary radiotherapy. On microscopic examination, all of the tumors had a complex papillary architecture with epithelial stratification and tufting. Six tumors were grade 2/3 and 11 were grade 3/3. All of the tumors had >10 mitotic figures per 10 high-power fields. An intense acute and chronic inflammatory infiltrate was typically present within the cores of the papillae and in areas of stromal invasion. Occasional psammoma bodies were present in three cases. Five of 12 tumors stained positively for p53, with six and nine of 12 tumors, respectively, immunoreactive for carcinoembryonic antigen and CA-125. Seven tumors were mixed with another histologic subtype of cervical adenocarcinoma, most commonly low-grade villoglandular adenocarcinoma. Fifteen patients were followed from 6 months to 11 years (mean 56 months). Six patients died of extensive metastases within 5 years of diagnosis; an additional patient experienced tumor recurrence with malignant ascites 2 years after diagnosis. The most common metastatic sites were pelvic and periaortic lymph nodes; other sites included cervical lymph nodes, lung, peritoneum, liver, and skin. Eight patients were alive without evidence of tumor at last follow-up. Age <65 years, stage >I, tumor size >2 cm, tumor invasion >10 mm, the presence of lymph node metastases, and elevation of serum CA-125 were associated with a poor prognosis. Tumor grade or composition (pure or mixed) did not correlate with patient outcome. Papillary serous adenocarcinoma of the cervix resembles microscopically its counterparts elsewhere in the female genital tract and peritoneum. The tumors can behave aggressively with supradiaphragmatic metastases and a rapidly fatal course when diagnosed at an advanced stage, but the outcome for patients with stage I tumors is similar to that of patients with cervical adenocarcinomas of the usual type.

Adult↗
PubMed1998

Immunohistochemical analysis of bcl-2, bax, mcl-1, and bcl-X expression in ovarian surface epithelial tumors.

Cell survival may be enhanced in tumors by the inhibition of apoptosis, which allows tumor promotors to exert their effects. The bcl-2 related genes have been shown to contribute to either the inhibition or induction of apoptosis in a variety of neoplasms; therefore, it was hypothesized that the expression of these genes might contribute to malignant transformation in ovarian surface epithelial tumors. The expression of bcl-2 family proteins was investigated in 28 ovarian surface epithelial tumors, including serous and mucinous benign, borderline, and malignant tumors by immunohistochemical staining with antibodies to bcl-2, bax, bcl-X, and mcl-1 proteins. Staining intensity was scored on a 1+ to 3+ scale and the benign, borderline, and malignant tumors were compared. Significantly less immunoreactive bcl-2 and bcl-X proteins were present in malignant serous tumors compared to their benign counterparts. No difference was seen in immunostaining for bax or mcl-1 when benign, borderline, or malignant serous tumors were compared. In the mucinous tumors, no differences were seen in immunostaining for any of the bcl-2 family proteins between tumor types. The loss of expression of the antiapoptotic proto-oncogenes bcl-2 or bcl-X in serous carcinomas compared to benign serous tumors, together with previous demonstrations that the presence of bcl-2 in ovarian surface epithelial cancers is a favorable prognostic indicator, suggests that bcl-2 and bcl-X have biological functions in the ovary other than inducing apoptosis, acting instead as tumor suppressor proteins.

Apoptosis↗
PubMed1998

Antioxidant gene expression in rat lung after exposure to cigarette smoke.

To investigate the effects of cigarette smoke on the expression of genes encoding intracellular antioxidant species, we exposed rats to whole cigarette smoke or air (control) daily for 1, 2, 7, or 14 days. After sacrifice, RNA was extracted from one lung and expression of mRNA for catalase (CAT), manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), glutathione peroxidase (GPX), and metallothionein (MT) was determined by Northern blots and dot blots. The anatomical distribution of expression of these genes was determined by in situ hybridization studies on sections of the contralateral lung. We found that expression of both MnSOD and MT was significantly increased (to levels 70 to 400% greater than in controls) at days 1 and 2 and returned to control levels by day 7. GPX expression was slightly but significantly increased at days 7 and 14 in smoke-exposed animals. CuZnSOD and CAT expression did not change from control levels. In control lungs, MnSOD was expressed in all cell types, with the highest expression seen in bronchial epithelial cells; a notable finding was a mosaic pattern of expression in the bronchial epithelium, with contiguous areas of bronchial epithelium composed of cells expressing MnSOD at high levels (hot spots), compared with the adjacent epithelium. In smoke-exposed lungs, the hot spots became less prominent after 1 and 2 days of exposure to smoke, but after 7 and 14 days the distribution of MnSOD expression was similar in control and smoke-exposed animals. CAT, CuZnSOD, GPX, and MT also showed widespread expression in the lung by in situ hybridization; GPX, CuZnSOD and MT were all most highly expressed in bronchial epithelium, whereas CAT expression levels were similar in all cell types. In contrast to MnSOD, expression of CAT, CuZnSOD, GPX, and MT was uniform within the bronchial epithelium, and the distribution of expression was the same in control and smoke-exposed animals at all time points. We conclude that most of these antioxidant enzymes and scavengers show prominent bronchial expression but that MnSOD shows a unique pattern, with intense hot spots in the epithelium of the small airways. This pattern is similar to the phenomenon of clonal heterogeneity described in other tissues but not previously reported in the lung. We conclude that cigarette smoke, like other forms of oxidant attack, transiently increases expression of MnSOD, and up-regulation of MnSOD expression appears to occur particularly in bronchial epithelial cells, which normally express MnSOD at relatively low levels. MT expression is also transiently increased by smoke whereas GPX expression increases after prolonged (7 to 14 days) exposure to cigarette smoke.

Animals↗
PubMed1997

Giant cell tumor of tendon sheath is a polyclonal cellular proliferation.

Giant cell tumor of tendon sheath (GCTTS) is a common soft tissue tumor. Immunophenotypical evidence suggests it is of synovial cell origin. There is controversy regarding the underlying nature of this lesion, specifically whether it is a neoplastic or nonneoplastic (ie, reactive or hyperplastic) process. Karyotypic abnormalities have been identified in GCTTS and interpreted as evidence of neoplasia, although the finding of similar karyotypic abnormalities in unequivocally nonneoplastic proliferations raises questions about using such findings to define a neoplasm. In an attempt to resolve this uncertainty, a polymerase chain reaction (PCR)-based assay for methylation of the X-linked human androgen receptor gene (HUMARA) was used to assess whether GCTTS is a clonal or polyclonal proliferation. DNA was isolated from formalin-fixed, paraffin-embedded tissue blocks from eight cases of digital GCTTS in female subjects; two cases of hepatocellular carcinoma (HCC) were used as clonal controls. Seven of eight cases of GCTTS were informative, and each showed a polyclonal proliferation, whereas both cases of HCC were clonal. Our results indicate that GCTTS is a nonneoplastic proliferation, if one accepts that a population of cells forming a tumorous mass must show clonality to be classified as a neoplasm. Our results emphasize that simple karyotypic abnormalities do not define a neoplasm. It remains to be determined whether GCTTS is a reactive or hyperplastic process.

DNA Methylation↗
PubMed1997

Large cell neuroendocrine [corrected] carcinoma of the uterine cervix: a clinicopathologic study of 12 cases.

Twelve cervical tumors showing morphologic evidence of neuroendocrine differentiation and lesional cells larger than those of typical small cell carcinoma are reported in women 21 to 62 (mean 34) years of age. The patients presented with an abnormal Papanicolaou smear or vaginal bleeding. Two tumors were stage Ia2, nine were stage Ib, and one was stage IIa. All patients were treated by radical hysterectomy, and most received adjuvant chemotherapy. Seven of 10 patients with > 1 year of follow-up died of tumor 6 to 24 months after hysterectomy. The tumors had insular, trabecular, glandular, and solid growth patterns and contained medium to large cells with moderate to abundant cytoplasm; eosinophilic cytoplasmic granules were present in nine cases. The tumors were mitotically active, and necrosis was present in 10 of them. Nine of 10 tumors were argyrophilic, and all 12 were immunoreactive for chromogranin. Individual cells containing somatostatin, serotonin, or glucagon were identified in four of eight cases. Adenocarcinoma in situ was present adjacent to the tumor in eight cases; invasive adenocarcinoma of non-neuroendocrine type was present in three of these tumors. Using diagnostic criteria established for pulmonary neuroendocrine tumors, the 12 tumors were classified as large cell neuroendocrine carcinomas. Cervical large cell neuroendocrine carcinomas are distinctive cervical carcinomas that are frequently misdiagnosed and have an unfavorable outcome, similar to that of small cell carcinoma.

Adenocarcinoma↗
PubMed1996

The Gfi-1 protooncoprotein represses Bax expression and inhibits T-cell death.

The Gfi-1 protooncogene encodes a nuclear zinc-finger protein that carries a novel repressor domain, SNAG, and functions as a position- and orientation-independent active transcriptional repressor. The Gfi-1 repressor allows interleukin 2 (IL-2)-dependent T cells to escape G1 arrest induced by IL-2 withdrawal in culture and collaborates with c-myc and pim-1 for the induction of retrovirus-induced lymphomas in animals. Here we show that overexpression of Gfi-1 also inhibits cell death induced by cultivation of IL-2-dependent T-cell lines in IL-2-deficient media. Similarly, induction of Gfi-1 in primary thymocytes from mice carrying a metal-inducible Gfi-1 transgene inhibits cell death induced by cultivation in vitro. The protein and mRNA levels of the proapoptotic regulator Bax are down-regulated by Gfi-1 in both immortalized T-cell lines and primary transgenic thymocytes. The repression is direct and depends on several Gfi-1-binding sites in the p53-inducible Bax promoter. In addition to Bax, Gfi-1 also represses Bak, another apoptosis-promoting member of the Bcl-2 gene family. Therefore, Gfi-1 may inhibit apoptosis by means of its repression of multiple proapoptotic regulators. The antiapoptotic properties of Gfi-1 provide a potential explanation for its strong collaboration with c-myc during oncogenesis.

Animals↗
PubMed1996

Analysis of germline and expressed T cell receptor variable region genes in Crohn's disease.

A possible role of the T cell receptor genes in the pathogenesis of Crohn's disease was investigated by 1) comparison of restriction fragment length polymorphisms at the T cell receptor beta chain locus in 64 Crohn's patients and 64 normal controls; 2) semi-quantitative polymerase chain reaction analysis of T cell receptor beta and alpha chain variable region gene expression by lamina propria lymphocytes from resected segments of diseased terminal ileum. We found no association between any of the restriction fragment length polymorphisms and Crohn's disease using polymorphic markers spanning the T cell receptor beta chain locus. Analysis of T cell receptor V beta and V alpha gene expression showed that expression of T cell receptor V region families in terminal ileum lymphocytes from patients with active Crohn's disease was indistinguishable from the lymphocytes found in normal terminal ileum. These data fail to support susceptibility to Crohn's disease being associated with the T cell beta chain antigen receptor genotype. No restricted or dominant T cell receptor variable region gene expression was found in Crohn's disease tissue, compared to normal terminal ileum.

Adult↗
PubMed1996

Detection of the EWS/WT1 gene fusion by reverse transcriptase-polymerase chain reaction in the diagnosis of intra-abdominal desmoplastic small round cell tumor.

We report two cases of intra-abdominal desmoplastic small round cell tumor with characteristic clinical, histological, immunohistochemical, and ultrastructural features. Fusion of the EWS gene on chromosome 22 and the WT1 gene on chromosome 11, resulting from the chromosomal translocation t(11;22)(p13;q12), was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in both cases. This translocation has been previously reported in this type of tumor using either cytogenetic or molecular biological techniques. Tumor tissue from both cases revealed no chimeric fusion transcripts characteristic of the Ewing sarcoma family of peripheral primitive neuroectodermal tumors or of alveolar rhabdomyosarcoma, two tumors in the differential diagnosis of intra-abdominal desmoplastic small round cell tumor. This report demonstrates the utility of molecular studies as an adjunct in the diagnosis of this rare and aggressive tumor.

Abdominal Neoplasms↗
PubMed1996

Radiation-induced atypia of endocervical epithelium: a histological, immunohistochemical and cytometric study.

Radiation-induced changes of the endocervical glandular epithelium have not been well characterized. Ten specimens (nine from hysterectomy, one from biopsy) from patients with therapeutic radiation to the pelvis for genitourinary or gastrointestinal cancer were examined by histological, immunohistochemical, flow cytometry and image cytometry analysis, and comparison was made to 10 cases of adenocarcinoma in situ (ACIS) of the cervix. Patients ranged from 34 to 68 years of age and received at least 3600 cGy total dosage to the pelvis. Hysterectomy or biopsy was performed six weeks to 17.5 years after completion of radiotherapy. Gross examination of the hysterectomy specimen revealed fibrosis, induration, stenosis, surface irregularity or an unremarkable cervix. Microscopic examination of endocervical glandular epithelium showed sparse, widely spaced glands which were tubular or dilated. Epithelium was simple cuboidal or flattened and consisted of large cells with at most a slight increase in N/C ratio, well-defined intercellular borders and eosinophilic or finely vacuolated cytoplasm. Nuclei frequently showed loss of polarity, one or two prominent eosinophilic nucleoli, and evenly dispersed chromatin; only occasional hyperchromatic cells were seen. Rare scattered cells were immunoreactive for carcinoembryonic antigen in seven of nine cases. One case was hyperdiploid by both flow cytometry and image cytometry. The remaining cases were diploid by flow cytometry and either diploid (five cases) or hypodiploid (four cases) by image cytometry. These findings indicate that pelvic radiation therapy causes characteristic histologic changes in endocervical glandular epithelium that are distinct from those of ACIS of the cervix. Cytoplasmic CEA staining frequently is focally positive and does not allow distinction from ACIS.

Adult↗
PubMed1996

Adenomyomas of the uterine cervix of of endocervical type: a report of ten cases of a benign cervical tumor that may be confused with adenoma malignum [corrected].

Ten benign biphasic cervical tumors that we have designated "adenomyomas of endocervical type" are reported because they might be confused with adenocarcinoma. The patients ranged from 21 to 55 years of age (mean, 40 yr). Two presented with abnormal vaginal bleeding, but, in most patients, the cervical tumors did not cause symptoms. On physical examination or at operation, eight patients were found to have tumors ranging from 1.3 to 8.0 cm in greatest dimension growing into the endocervical canal and, in three cases, prolapsing through the external os. The remaining two patients had mural tumors measuring 11.0 and 23.0 cm in greatest dimension, which projected into the pelvis from the outer aspect of the cervix, without mucosal involvement. The tumors were well circumscribed and grey-white or tawny, and five contained multiple mucin-filled cysts up to 3.0 cm in diameter. One tumor was focally hemorrhagic. On microscopic examination, the tumors were composed of glands and cysts lined by a single layer of endocervical-type mucinous epithelium admixed with smooth muscle. The epithelial component was typically composed of large irregularly shaped glands with papillary epithelial infolding, surrounded by smaller simple glands, frequently resulting in a lobular arrangement. Tubal-type epithelium was present focally in six tumors and endometrial-type glands surrounded by endometrial stroma were present in one case. Both the epithelium and smooth muscle were uniformly bland, without significant mitotic activity. Five patients were treated initially by "polypectomy." Hysterectomy 1 month and 1 year later in two of the cases revealed residual adenomyoma; a "recurrence" 3 years after polypectomy in another patient was treated by hysterectomy. In no case has there been evidence of spread beyond the cervix. The finding of a cervical tumor composed of bland, irregularly shaped, mucinous glands surrounded by smooth muscle caused significant problems in differential diagnosis and a diagnosis of adenoma malignum was either favored or raised as a possibility by the initial pathologist in five of the cases. The gross circumscription of the adenomyomas, their polypoid appearance, the frequent lobular arrangement of glands, the absence of invasive glands with a desmoplastic stromal reaction, and lack of even focal atypia were the most helpful findings in differentiating these tumors from adenoma malignum.

Adenocarcinoma↗
PubMed1995

Chromosomal localization of a gene, GF1, encoding a novel zinc finger protein reveals a new syntenic region between man and rodents.

The Gfi1 gene encodes a zinc finger protein which binds DNA and is involved in transcriptional regulation. Gfi1 was assigned to the central portion of mouse Chr 5 by interspecific backcross mapping and to human chromosome band 1p22 and rat chromosome band 14p22 by fluorescence in situ hybridization (FISH). Comparative mapping data presented here describes a new syntenic region between man and rodents.

Animals↗
PubMed1995

Prolactin (PRL)-dependent expression of a zinc finger protein-encoding gene, Gfi-1, in Nb2 lymphoma cells: constitutive expression in autonomous sublines.

The proliferation of cultured rat Nb2 lymphoma cells is dependent on prolactin (PRL) acting as the principal growth factor. Previously, PRL-independent Nb2 sublines were obtained by PRL starvation of the parent line and cloning of surviving cells. Development of PRL independence was in some cases found to be associated with a reciprocal translocation involving chromosome 14 at breakpoint 14p22. In the present study, a novel, 14p22 zinc finger protein-encoding gene, Gfi-1, has been examined for a role in Nb2 cell proliferation. PRL-dependent Nb2 cells expressed the gene during active growth; in comparison, in stationary, early G1-arrested cells obtained by an 18 hr lactogen starvation, Gfi-1 gene expression was markedly decreased. Addition of PRL to such stationary cells led to induction of Gfi-1 gene expression within a few hr with a maximum in late G1. Actively growing cells from 5 different PRL-independent Nb2 sublines, cultured in chemically defined, mitogen-free medium, expressed the gene constitutively. In two sublines, carrying the 14p22 rearrangement, the gene was markedly overexpressed. The results suggest the Gfi-1 gene product has a regulatory role in Nb2 cell mitogenesis and that unscheduled activation could contribute to loss of PRL dependency.

Animals↗
PubMed1995

Screening for urothelial malignancies by cytologic analysis and flow cytometry in a community urologic practice: a prospective study.

A prospective study was initiated to compare the ability of flow cytometry and cytologic analysis to detect malignant cells in urine obtained at the time of cystoscopy. The population studied consisted of patients from general urologic practices who were undergoing cystoscopy in a single community hospital. Over a 1-yr period, 335 specimens from 317 patients were studied. Nineteen biopsy-proven urothelial malignancies were identified. Cytologic examination of urine obtained at the time of cystoscopy was positive in seven of these cases, and an aneuploid population of cells was identified by flow cytometry in three cases. All three cases of high-grade transitional cell carcinoma and carcinoma in situ were correctly identified by the combination of cytologic examination and flow cytometry; however, only four of 16 low-grade superficial papillary transitional cell carcinomas were recognized cytologically, with only one being aneuploid. The combination of cytologic analysis and flow cytometry did not increase the diagnostic sensitivity above that achieved with cytologic testing alone (overall sensitivity, 37%). We conclude that flow cytometry and cytologic analysis, either individually or in combination, are too insensitive for use in a routine screening program for urothelial malignancy in a community hospital setting because of the inability of either method to detect low-grade transitional cell carcinomas reliably.

Carcinoma, Squamous Cell↗
PubMed1994

Small-cell carcinoma of the endometrium. A clinicopathological study of sixteen cases.

Sixteen cases of small-cell carcinoma of the endometrium were encountered in patients who ranged in age from 30 to 78 (mean, 57.4) years. Of the 12 patients whose presenting features are known, eight had abnormal vaginal bleeding, three had pain related to metastatic tumor, and one patient had both symptoms. On pelvic examination, adnexal masses were palpable in three patients, and vaginal involvement was evident in two; one patient had a large palpable periumbilical mass. Thirteen patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Extrauterine spread was documented intraoperatively in eight cases, including widespread intraabdominal and ovarian metastases in four cases, vaginal involvement in the two cases noted previously, paraaortic lymph node involvement in one case, and tubal involvement in one case. Three tumors were International Federation of Gynecology and Obstetrics (FIGO) stage I, four were stage II, two were stage III, and six were stage IV; in one case, there was insufficient information to allow staging. On gross examination, the tumors were usually described as bulky, ill-defined, and invasive of the myometrium; four were polypoid. Microscopic examination revealed sheets, cords, and nests of small or intermediate-sized cells with scanty cytoplasm, hyperchromatic nuclei, and a high mitotic rate. Single-cell and zonal necrosis and vascular invasion were typically present. Synchronous grade 1 or grade 2 endometrial endometrioid adenocarcinoma was present in eight cases, and complex atypical endometrial hyperplasia, in two others. In three cases, the adenocarcinoma merged almost imperceptibly with the small-cell component. None of the tumors contained argyrophil or argentaffin cells, although nine of 11 tumors were immunoreactive for neuron-specific enolase (one of these was also Leu-7 positive), and another was chromogranin positive. Of the 11 cases with follow-up information, seven patients died of disease (at least four with distant metastases) with a median survival of 12 months, and another patient was alive with distant metastases at 18 months. The remaining patients were clinically free of disease at postoperative intervals of < or = 1 year (two cases) and 4.5 years (one case). This study confirms that small-cell carcinomas of the endometrium are a histologically distinctive subtype of endometrial carcinoma, which, like their counterparts in the uterine cervix, are aggressive tumors with a propensity for systemic spread and a poor prognosis.

Adenocarcinoma↗
PubMed1994

T cell receptor gene expression and genotypes in celiac disease.

Celiac disease (CD) occurs as a result of an abnormal immune response, within the mucosa of the small bowel, to dietary gliadin peptides. To further characterize the intramucosal lymphocytes in patients with untreated CD, we compared T cell receptor (TCR) variable region gene expression in small bowel biopsies from patients with CD to that of normal small bowel. We also assessed TCR genotypes, using restriction fragment length polymorphisms (RFLPs) spanning the V beta gene locus, comparing 59 CD patients to 64 normals. The abnormal immune response in CD is polyclonal, without evidence of restriction or significantly increased expression of any TCR variable region gene families, compared to normal small bowel. No significant association was found between TCR genotypes, as defined by TCR V beta RFLPs, and CD.

Adult↗
PubMed1994

Idiopathic granulomatous mastitis. A report of three cases and review of the literature.

We report three cases of idiopathic granulomatous mastitis that occurred in women of reproductive age (range, 25 to 36 years). These patients presented with breast masses of 2.5, 7, and 10 cm. One patient also had erythema nodosum. On biopsy specimens, the characteristic histopathologic features of granulomatous inflammation, centered on mammary lobules, were present in each case. In only one case was a specific diagnosis of granulomatous mastitis rendered based on the results of the biopsy; this patient received oral prednisone with prompt shrinkage of the breast mass to 20% of its original size. This residual mass was then resected. The remaining two patients were observed after biopsies were performed, with one experiencing a local recurrence after 5 weeks. The optimal therapy for idiopathic granulomatous mastitis has not been established, and we discuss treatment options, based on these three cases and those previously reported.

Adult↗