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An open trial of valproate in borderline personality disorder.

BACKGROUND: Target symptoms in pharmacotherapy of borderline personality disorder include mood instability, anxiety, and impulsivity. Valproate appears useful for the treatment of these target symptoms in several disorders, and carbamazepine has been found effective for such symptoms in borderline personality disorder. We therefore conducted a preliminary open-label trial of valproate in borderline personality disorder. METHOD: Eleven patients who met DSM-III-R criteria for borderline personality disorder were entered into an 8-week study of valproate. Exclusion criteria included current major depression or major medical disorder. All patients were in psychotherapy at least once a week for a minimum of 8 weeks prior to starting medication. Valproate was increased as tolerated to reach blood levels of 50 to 100 micrograms/mL. Clinician- and self-rated scales were completed each week. RESULTS: Three patients did not complete the study. Of completers, 4 of 8 patients were responders ("much less" or "less") on clinician-rated change scores for overall pathology and for mood. Three of 8 patients were responders on change scores for anxiety, anger, impulsivity, and rejection sensitivity. There was a significant (p = .03) decrease in total Symptom Checklist-90 scores between the start and end of the trial. On the Overt Aggression Scale (Modified), total other-directed assault did not significantly decrease, but there was a significant (p = .02) decrease in global subjective irritability. CONCLUSION: Valproate led to overall improvement in 50% of a small sample of borderline personality disorder patients who completed an 8-week open trial. The medication was modestly helpful for mood and irritability as well as for anxiety, anger, rejection sensitivity, and impulsivity, but specific therapeutic effects varied from patient to patient. More extensive controlled trials of anticonvulsants for impulsive personality disorders are warranted.

Adult↗

[The borderline patient. Diagnosis, psychodynamics and physician-patient relation].

'Borderline' is a popular psychiatric diagnosis. The uses of the term are variable and often unclear. It is the goal of this presentation to elaborate a borderline concept for use in daily clinical practise. First, development of the term over the preanalytical, analytical and empirical areas is summarized. Next, the term of borderline for clinical practise is developed on the basis of characteristics and the global picture. Characteristics are: intensive, instable behaviour in relations, reduced control of impulse, disturbed affection and mood, psychotic manifestations, instable social adaptation. Diagnosis is founded on exploration of characteristics and on seizing of the global picture. The combination with other psychiatric disorders and separation from other personality disorders have to be considered with respect to differential diagnosis. The descriptive diagnosis has to be complemented from a psychodynamic point of view. The borderline patient has in his psychologic development failed to segregate sufficiently from his primary reference person. This results in a structural deficit and a weak ego. This latter is characterized by deficient integration and deficient separation, by disturbed perception of reality and by a non-specific general weakness of the ego. Finally, difficulties arising in the relations between physician and borderline patient are outlined.

Affect↗

Vomiting as a manifestation of borderline personality disorder in primary care.

BACKGROUND: Patients with borderline personality disorder often are found and treated in psychiatric settings following episodes of self-mutilation, such as wrist-slashing. Family physicians care for many patients with borderline personality disorder, but in primary care settings wrist-slashing or other physical mutilation is a less common presenting problem. Frequently these patients complain of such symptoms as nausea and vomiting that do not so obviously suggest psychopathology. METHODS: Three primary care patients with borderline personality disorder in whom episodic vomiting was the chief complaint are presented. Hypotheses from the literature about the neurobiology of vomiting and self-mutilation are discussed. RESULTS: Vomiting is a primary care analogue of self-mutilation in some patients with borderline personality disorder. CONCLUSIONS: Family physicians should include careful history taking to corroborate other features of borderline personality disorder in evaluating patients with persistent, episodic vomiting. Obtaining a history of early sexual abuse or chronic interpersonal problems as an adult should not only mitigate the compulsion for extensive, costly, and invasive gastrointestinal system evaluations in such patients, but also suggest more effective treatment strategies.

Adult↗

[Fluoxetine in the treatment of borderline personality disorder].

OBJECTIVE: This study evaluates the therapeutic effect of fluoxetine, a selective serotonin reuptake inhibitor, in borderline personality disorder. METHOD: 46 patients with borderline personality disorder according to DSM-III-R and Diagnostic Interview for Borderlines (DIB-R) criteria, were given fluoxetine 20-60 mg for seven weeks. They were evaluated each week using Brief Psychiatric Rating Scale (BPRS), Global Assessment of Functioning Scale (GAF), Hamilton Depression Rating Scale (HDRS) and a clinical Impulsivity Scale. RESULTS: There were significant improvements in BPRS, HDRS, GAF and Impulsivity Scale from the first week of the treatment. These improvements continued until the seven week of treatment. The favourable outcome was not only due to the improvement in depression and impulsivity scores, but also to the decline of global psychopathology. CONCLUSIONS: The data suggest that fluoxetine is an effective pharmacologic treatment for borderline personality disorder. These findings support the hypothesis of a 5-HT dysfunction in borderline personality disorder.

Adolescent↗

The role of DNA flow cytometry in borderline malignant ovarian tumors.

BACKGROUND: The role of flow cytometric DNA analysis in predicting prognosis of patients with borderline malignant ovarian tumors has been controversial. METHODS: Fifty cases of patients with borderline malignant ovarian tumors were analyzed by histology and by flow cytometry on paraffin embedded tissue. Multiple tissue blocks and serial sections were analyzed for each tumor. The results of DNA analysis were correlated to clinicopathologic data. RESULTS: DNA aneuploidy was demonstrable in 4 cases (8%) when the most atypical section was analyzed. The overall rate of aneuploidy was 14% if additional blocks and serial sections were studied. Two patients died from tumor. One of the two patients had an initial diagnosis of Stage IIc mucinous borderline tumor with DNA indices (DI) of 1.12, 1.42, and 2.04. She had a recurrence in the contralateral ovary 1 year later (DI = 1.83), and a second frankly malignant recurrence diffusely in peritoneum (DI = 1.89). The other patient had an initial diagnosis of Stage IIIc mucinous borderline ovarian tumor with pseudomyxoma peritonei. DNA diploidy was obtained in all of the samples from the primary tumor. An aneuploid peak (DI = 1.28) was demonstrated in only one serial section of the peritoneal implants. Of the other 5 patients who had aneuploid histograms but were disease-free, the DNA indices were 1.35, 1.14/1.18, 1.15, 1.20, and 1.31 and were demonstrable only in either 1 or 2 of the blocks or unproven on serial sections. All patients with diploid-peridiploid tumors were alive and disease free. CONCLUSIONS: Reproducible DNA aneuploidy of high DI may be predicting a poor outcome, whereas the significance of inconsistently reproducible aneuploidy of low DI remains to be determined. Further studies of prospective DNA analysis with adequate sampling are necessary to define the role of flow cytometry in patients with borderline malignant ovarian tumors.

Adolescent↗

Serous borderline tumors of the ovary with noninvasive peritoneal implants.

BACKGROUND: The authors conducted this study to update their experience with patients who have ovarian serous borderline tumors with noninvasive peritoneal implants, with the objectives of gaining additional insight into the biologic behavior of these tumors and understanding better the effects of postoperative treatment. METHODS: Seventy-three patients who had ovarian serous borderline tumors with noninvasive peritoneal implants were identified in a retrospective review. Major end points selected for analysis were surgicopathologic response, time to relapse, type of relapse, progression free survival, and overall survival. Univariate and multivariate regression analyses were also performed. RESULTS: The median follow-up time was 10.3 years. Of 20 patients with macroscopic residual disease at completion of initial surgery who subsequently underwent second-look surgery, 3 (15%) had a response to chemotherapy. Twenty-two of 73 patients (30%) either developed progressive disease or had a relapse. The median time from the date of diagnosis to relapse was 7.1 years. Tissue was available from 20 of the 22 patients who had a relapse; 14 (70%) had invasive low grade serous carcinomas, and 6 (30%) had recurrent borderline tumors. Age was the only factor studied that had a significant influence on survival (P = 0.03). In both univariate and multivariate proportional hazards models, age and residual disease were found to be of borderline significance in predicting cancer specific survival. CONCLUSIONS: Approximately 30% of patients who have ovarian serous borderline tumors with noninvasive peritoneal implants will develop progressive or recurrent tumors, most commonly serous carcinomas. The presence of macroscopic residual disease appears to be a predictor of disease free survival. In this study, however, the authors were unable to elucidate the role of postoperative therapy or determine criteria for selecting patients for such therapy.

Adolescent↗

Mucin gene transcripts in benign and borderline mucinous tumours of the ovary: an in situ hybridization study.

Mucinous tumours of the ovary are characterized by mucin-secreting cells exhibiting a variable endocervical, intestinal, gastric or pancreatobiliary phenotype as ascertained by microscopy, electron microscopy, histochemistry or immunohistochemistry. The molecular mechanisms underlying the tumourigenesis process are not well understood. The mucin glycoproteins expressed by ovarian mucinous tumours have not been fully characterized, but mucins are known to be implicated in tumour progression in various epithelial neoplasms. The purpose of this study was to evaluate the expression of mucin genes (MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6) in ovarian mucinous tumour cells, to relate MUC gene expression to the histological diagnosis, and to compare the expression patterns with those observed in normal tissues. The expression of mucin genes was evaluated by in situ hybridization in 21 mucinous tumours (11 adenomas and ten borderline tumours). Heterogeneity of expression correlated with morphological heterogeneity. Intense expression of the MUC5AC gene, suggesting a gastric surface cell phenotype, was demonstrated in 18/21 tumours (86%). Goblet cells expressing the MUC2 gene and columnar cells expressing the MUC3 gene were consistent with an intestinal phenotype, which was observed in 15 tumours (71%) including nine adenomas and six borderline tumours. Major expression of MUC4 and MUC5B consistent with an endocervical phenotype was observed in seven benign (64%) and three borderline (30%) tumours. In all, the MUC profiles suggested gastrointestinal-type cells in 13 cases (62%), gastric-type cells in five cases (24%), and intestinal-type cells in two cases (one benign, one borderline) (9%); the results were inconclusive in one borderline tumour (5%). It is concluded that gastric and, to a lesser degree, intestinal differentiation are early and almost constant events in ovarian mucinous tumourigenesis.

Adolescent↗

Ovarian mullerian mucinous papillary cystadenomas of borderline malignancy. A clinicopathologic analysis.

Ovarian mucinous cystadenomas of borderline malignancy that contain foci of intestinal differentiation are well recognized. Borderline tumors lined by mucinous epithelium of endocervical type and characterized by papillae architecturally similar to those of serous borderline tumors, however, have not been described in the literature. We have studied 30 tumors of this type. The patients averaged 34 years of age. Forty percent of the tumors were synchronously bilateral and 30% were associated with endometriosis. Four tumors were complicated by peritoneal implants, one by both peritoneal implants and lymph node metastasis and one by lymph node metastasis alone. No patient had pseudomyxoma peritonei. Follow-up information was available on all the patients for a mean interval of 3.7 years. In two cases tumors developed in the conserved contralateral ovary; no deaths occurred. These tumors have important clinical and pathologic differences from mucinous borderline tumors with intestinal differentiation, but have many similarities to mixed-epithelial borderline tumors of Mullerian type.

Adult↗

Quantitative nuclear morphology in the diagnosis of ovarian tumors of low malignant potential (borderline).

Ovarian tumors of low malignant potential or of borderline malignancy are characterized histologically by the association of malignant type of epithelial proliferation with a noninvasive pattern of growth. Because epithelial proliferation relates to features of nuclear morphology and chromatin structure and because of the difficulties to distinguish nuclear atypism seen in borderline malignancy from that in frankly invasive tumors by usual microscopic study, the authors concentrated their studies exclusively on computerized analysis of cell nuclei images. Using specially developed methods of analysis the authors described geometrical, optical, and structural differences among the epithelial and stromal cell nuclei of benign, borderline, and malignant ovarian tumors. The structural differences concern the pattern of chromatin condensation and suggest that the cytokinetic properties of the borderline tumors are intermediate to those of benign and malignant. The results demonstrate that the quantitative evaluations provide objective and reproducible data useful in the differential diagnostic of the borderline malignancy.

Adenoma↗

The borderland between benign and malignant surface epithelial ovarian tumors. Current controversy over the nature and nomenclature of "borderline" ovarian tumors.

In the early 1970s, the International Federation of Gynecology and Obstetrics (FIGO) and the World Health Organization (WHO) adopted the terms "borderline malignancy" and "carcinoma of low malignant potential" in their classifications of surface epithelial tumors of the ovary in order to denote a subset of patients with a significantly more favorable prognosis than those with the "usual" surface epithelial carcinomas. Subsequently, a considerable clinicopathologic body of literature has arisen concerning borderline tumors, particularly the serous and mucinous types. Some of them, particularly advanced stage borderline tumors, have been purported to cause significant illness and death. However, some investigators have impugned their malignant nature, especially in Stage I disease, and blame the suggested poor prognosis in advanced cases on a paucity of accurate morbidity and mortality data and ambiguity in current histopathologic terminology; to address the latter, they have proposed to remove any connotation of malignancy by replacing the aforementioned terms with designations such as "atypical proliferating (serous or mucinous) tumor." Another soon-to-be proposed classification will use the terminology "borderline tumors" as a generic group without destructive invasion but with subdivisions into tumors with "epithelial atypia" and those with "intraepithelial carcinoma." The clinical and therapeutic implications of accurate diagnosis of ovarian borderline tumors mandate additional investigation to elucidate their true prognosis; indeed, further dialogue is necessary to arrive at a nosologic system to reflect that biologic behavior. However, until a consensus has been reached, the pathologic diagnosis should reflect, at some point, the currently sanctioned FIGO/WHO classification of surface epithelial ovarian tumors to obviate any misunderstanding that could lead to patient mismanagement.

Female↗

Infertility treatment after conservative management of borderline ovarian tumors.

BACKGROUND: Young patients with ovarian tumors of low malignant potential usually undergo conservative surgery because of the excellent prognosis of these tumors. Patients wishing to conceive after diagnosis occasionally require ovulation induction, but data regarding the safety of assisted reproductive technologies in this situation remains anecdotal. The current study analyzes the outcome of a group of patients who received infertility treatment after the conservative management of borderline ovarian tumors. METHODS: The clinical and pathologic records of 104 patients with a borderline tumor of the ovary who were treated and followed over a 20-year period (1979--1999) were reviewed. Forty-three patients who underwent conservative management were the subjects of the current study. RESULTS: Follow-up was available for 95% of the patients, giving a total of 270 women-years of follow-up. Nine of the 43 patients developed a local recurrence, 8 of which occurred in patients with serous tumors. Five of these 9 patients underwent cystectomy only at the time of recurrence, and all were without evidence of disease at a mean follow-up of 75 months (range, 25--93 months). Nineteen patients delivered a total of 25 healthy children after diagnosis of a borderline ovarian tumor; 7 of these patients were treated with in vitro fertilization (IVF) after diagnosis. Four of these patients developed a recurrence, two patients before the IVF treatment and two patients after the IVF treatment. The latter two patients were without evidence of disease at the time of last follow-up (15 months and 26 months, respectively, after the recurrence). CONCLUSIONS: The results of the current study suggest that ovulation induction may be considered after the diagnosis of a borderline ovarian tumor. Recurrences were observed in two of seven patients, all of which remained histologically borderline.

Adolescent↗

Relationship of borderline syndrome disorders to early schizophrenia on the MMPI.

An intriguing question in modern psychopathology is the relationship of borderline syndrome disorders to other psychopathological conditions and to each other. The present study compared groups of DSM-III defined Borderline Personality Disorder (N = 51), Schizotypal Personality Disorder (N = 14), and Mixed Borderline-Schizotypal Personality Disorder (N = 17), with CATEGO diagnosed Schizophrenic Disorder of recent onset (N = 30) and nonpsychiatric controls (N = 20) on the MMPI. Profile and individual scale analyses revealed gross elevations on multiple scales in each of the patient groups, as compared with controls. Subtle differences in test performance between the borderline personality and schizotypal personality groups are noted and are consistent with their separation as disorders in DSM-III. Multivariate profile analyses distinguished the borderline, schizotypal, and early schizophrenic groups from each other, but not from the mixed personality group. Thus, this latter group may serve to bridge these diverse populations.

Adolescent↗

Surgery for borderline tumor of the ovary.

The five-year survival for women with Stage I borderline tumors is about 95% to 97%, but because of late recurrence the 10-year survival is only 70% to 95%. The five-year survival for Stage II-III patients is 65% to 87%. A more correct staging procedure, classification of true serous implants, and agreement on how the presence of gelatinous ascites in mucinous tumors contributes to cancer stage might change the distribution of stage and survival data by stage for women with borderline tumors in the future. Independent prognostic factors for patients with borderline tumors without residual tumor after primary surgery are: DNA ploidy, morphometry, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, and age. Different types of surgery and chemotherapy were not independent prognostic factors. Questions which should be addressed include the following: 1) Have patients with borderline tumors been over treated in general, and how should these patients be treated? 2) In which group of patients is fertility-sparing surgery advisable? 3) Do patients with borderline tumors benefit from adjuvant treatment? And 4) How is the high-risk patient defined?

Carcinoma↗

Serum lipase levels as a diagnostic marker in cystic fibrosis patients with normal or borderline sweat tests.

Patients with normal or borderline sweat test present a diagnostic challenge. In spite of the availability of different methods such as genetic analysis and measurements of nasal potential difference, uncertainty in diagnosing cystic fibrosis (CF) in some patients still exists. Neonates with CF have high serum lipase levels, which decline over time in pancreatic-insufficient patients, whereas pancreatic-sufficient patients demonstrate high serum lipase levels beyond infancy. Because patients with borderline or normal sweat test are almost always pancreatic sufficient, this study was aimed to assess whether serum lipase levels may be of help in establishing the diagnosis of CF in these patients. Serum lipase levels were measured in 100 CF patients and in 17 healthy individuals. Patients were grouped according to their genotype. Group A patients (n = 70) carried two mutations previously found to be associated with a pathologic sweat test and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R). Group B (n = 30) were compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat tests and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 17 healthy controls. Serum lipase levels ranged between 2 and 104.4 U/L (mean +/- SD 16.9 +/- 14.7), 6.1-200 U/L (mean +/- SD 53.9 +/- 47.9), and 8.5-27.8 U/L (mean +/- SD 16.9 +/- 5.1) in Groups A, B, and C, respectively, with some overlapping between groups. The distribution of lipase levels was significantly different in Group B vs Groups A and C (P < 0.01). High lipase levels were found in 63.3% (19/30) of Group B patients, but in only 4.3% (3/70) and 0% (0/17) of Group A and C, respectively. Lipase levels were found to be inversely related to sweat chloride concentrations (r = -0.19, P < 0.05). Patients with borderline or normal sweat tests had high lipase levels, whereas low lipase levels were associated with pathologic sweat tests. Our findings indicate that the serum lipase level is genetically determined and that it has a useful role in the diagnosis of CF. Thus, in patients with borderline sweat tests and high lipase levels, the diagnosis of CF should be considered.

Adult↗

Restaging surgery for women with borderline ovarian tumors: results of a French multicenter study.

BACKGROUND: The purpose of the current study was to examine the surgical management of women with borderline ovarian tumors and the adequacy of initial staging according to the guidelines of the International Federation of Gynecology and Obstetrics; to evaluate the impact of restaging operations; and to identify risk factors for initial understaging. METHODS: In a retrospective French multicenter study, 54 of 360 women with borderline ovarian tumors underwent a restaging operation. After excluding women with initial complete staging (n = 62), epidemiologic, surgical, and histologic parameters and risk of recurrence were compared between women who underwent restaging (n = 54) and those who did not (n = 244). RESULTS: One hundred fifty (41.6%) of 360 women underwent intraoperative histologic examination, which led to the diagnosis of a borderline tumor in 97 cases (64.7%). Thirty-seven (38.1%) of these 97 women had undergone complete initial staging procedures. A restaging operation was performed for 54 women. A lower median age and a higher rate of conservative treatment were noted in the group that underwent restaging. Eight (14.8%) of the 54 women who underwent restaging had their tumors upstaged: 7 of the 41 cases initially diagnosed as Stage IA tumors were upstaged to Stage IB (n = 3) or to Stage IIA, IIB, IIIA, or IIIC (n = 1 for each); in the eighth case, a Stage IC tumor was upstaged to Stage IIIA. Upstaging tended to be more common in women with serous borderline tumors (P = 0.06) and in women who underwent cystectomy (P = 0.08). There was no difference in recurrence rates according to whether a restaging operation was performed. The recurrence rates after conservative and radical treatment were 15.6% (25 of 160) and 4.5% (9 of 200), respectively (P < 0.001). CONCLUSIONS: Women who initially were diagnosed with Stage IA disease and who had serous borderline tumors or underwent cystectomy appeared to derive the most benefit from restaging surgery. Nonetheless, the indications for restaging surgery remain controversial, as no difference in recurrence rate was observed between women who underwent restaging and those who did not.

Adult↗

Computerized image analysis and flow cytometric evaluation of ovarian borderline tumors: a study of 24 cases.

DNA content evaluation in the study of ovarian borderline tumors has been shown to be a useful adjunct to histopathologic diagnosis. This study compares flow cytometry and computerized image analysis (CIA) in evaluating the DNA content of these lesions. Twenty-four cases of ovarian borderline tumors (15 serous, 9 mucinous) were studied utilizing formalin-fixed paraffin-embedded tissue. Flow cytometry of cell suspensions and CIA of cell suspensions and paraffin sections were compared in the evaluation of DNA content. Twenty-three tumors (96%) were diploid and only 1 (4%) was aneuploid. There was 100% correlation between flow cytometry and CIA of cell suspensions. Image analysis of Feulgen-stained paraffin sections was found to be unreliable when compared with the use of cell suspensions in the evaluation of DNA content. Clinical follow-up in 17 patients showed recurrent disease in two patients with diploid tumors and no evidence of disease in the patient with an aneuploid tumor. The reported rate of aneuploidy in borderline tumors varies depending on the diagnostic method employed in evaluating DNA content. This study shows good correlation between flow cytometry and image analysis of cell suspensions and supports the low rate of aneuploidy found in these lesions by other authors utilizing these methods. The majority of borderline ovarian tumors have been shown to have a diploid DNA content; however, the finding of aneuploidy in histologically classified borderline tumors warrants close clinical follow-up since aneuploidy in these tumors has been associated with an adverse prognosis.

Aneuploidy↗

Expression of BRCA1 protein in benign, borderline, and malignant epithelial ovarian neoplasms and its relationship to methylation and allelic loss of the BRCA1 gene.

BRCA1 is a putative tumour suppressor gene responsible for a hereditary ovarian cancer syndrome. To clarify the possible involvement of BRCA1 in the development of sporadic ovarian neoplasms, this study analysed the immunohistochemical expression of BRCA1 protein in normal ovarian surface epithelium and 119 epithelial ovarian tumours (19 benign, 24 borderline, and 76 malignant tumours). Loss of heterozygosity (LOH) of BRCA1 was examined using three microsatellite markers to analyse the relationship between BRCA1 expression and alterations of the BRCA1 gene. Methylation of the BRCA1 promoter was also analysed by methylation-specific PCR. In ovarian carcinomas showing heterogeneous expression of BRCA1 protein in the same tumour, LOH and methylation status were analysed using microdissection techniques. Finally, the relationship of BRCA1 expression or its genetic alteration to clinicopathological parameters and patient survival was analysed. Ovarian surface epithelial cells expressed BRCA1 protein. Decreased expression of BRCA1 was found in 16% of benign tumours, 38% of borderline tumours, and 72% of carcinomas. LOH of BRCA1 was demonstrated in no benign tumours, 15% of borderline tumours, and 66% of carcinomas. Methylation of BRCA1 was not detected in benign or borderline tumours, but was present in 31% of carcinomas. Reduced expression of BRCA1 correlated with the presence of gene methylation. The frequency of BRCA1 methylation and LOH was higher in serous carcinomas than in other types. In one of the three serous carcinomas that showed heterogeneous expression of BRCA1, BRCA1-positive borderline-like tumour cells were LOH-positive and methylation-negative, whereas adjacent BRCA1-negative carcinoma cells were LOH-positive and methylation-positive. The prognosis of carcinoma patients did not correlate with BRCA1 expression or genetic status. These findings suggest that reduced expression of BRCA1 protein along with genetic and epigenetic changes of the BRCA1 gene play an important role in the development of sporadic ovarian carcinomas, particularly those of serous histology.

Adult↗

Expression of GLUT-1 glucose transporter in borderline and malignant epithelial tumors of the ovary.

OBJECTIVE: Cancer cells have increased rates of glucose metabolism when compared to normal cells. One of the mechanisms proposed for the accelerated glucose use in malignant cells is the overexpression of glucose transporters. In this study we evaluated the expression of the GLUT-1 glucose transporter in borderline and malignant epithelial neoplasms of the ovary. METHODS: Histologic sections of tumor tissues from 21 borderline and 82 malignant epithelial neoplasms of the ovary were stained for GLUT-1 using polyclonal GLUT-1 antibody (Dako, Carpinteria, CA) and the labeled streptavidin biotin procedure. DAB was used as chromagen and tissues were counterstained with hematoxylin. RESULTS: Normal ovarian surface epithelial cells were either negative or weakly positive. Of the 82 carcinomas, 81 (98.8%) were positive for GLUT-1. The staining intensity was significantly associated with the grade of tumor (P = 0.001). Of the 21 borderline neoplasms, 20 (95.2%) were positive for GLUT-1. Carcinomas had a significantly stronger stain than borderline tumors (P = 0.0001). The intensity of the stain was also stronger in serous carcinomas compared to other subtypes (P = 0. 0001). Positive cells demonstrated a cytoplasmic membrane staining that was more intense in tumor cells farther away from blood supply. CONCLUSION: Overexpression of the GLUT-1 transporter is associated with the histology and grade of the tumors. Our findings show a progressive increase in the expression of the GLUT-1 transporter from the borderline tumor to the high-grade carcinomas. These data suggest that the expression of this transporter may be closely related to the malignant transformation of epithelial ovarian tumors.

Cell Membrane↗