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Biomedical subjects

C Silfverswärd

Publications and source records attributed to C Silfverswärd.

At least 19 recordsLinked to original sources

Laminin-5 gamma2-chain expression and DNA ploidy as predictors of prognosis in endometrial carcinoma.

Expression of the laminin-5 gamma2-chain in carcinoma cells has been implicated in tumor invasion. The aim was to investigate the expression and prognostic significance of the ln-5 gamma2-chain compared with clinicopathological factors and tumor cell DNA ploidy in endometrial carcinoma. Histological specimens from 80 endometrial carcinomas were examined with respect to immunohistochemical ln-5 gamma2-chain expression and correlated to the clinicopathological characteristics, DNA ploidy, and survival. Sixty-eight of 80 investigated cases were judged to be positive for the ln-5 gamma2-chain. Ln-5 gamma2-chain did not show any correlation to stage, histopathological subtype, grade, and DNA ploidy. In univariate analyses, advanced stage (p < 0.001), nonendometrioid carcinoma (p = 0.030), low grade (p < 0.001), aneuploid tumors (p < 0.001), and ln-5 gamma2-chain expression (p = 0.017) were highly associated with poor survival. Aneuploid tumors in combination with strong ln-5 gamma2-chain expression were significant predictors (p < 0.001) of poor prognosis. In multivariate analyses including stage, histopathological subgroup, grade, DNA ploidy, and ln-5 gamma2-chain expression, all lost their significant prognostic information except for stage (p < 0.001) and grade (p < 0.05). Ln-5 gamma2-chain expression and DNA ploidy both as a single parameter and in combination were demonstrated to be signifi- cant prognostic factors in univariate analysis. However, stage and grade provided more useful clinical information beyond histopathological subgroup, DNA ploidy, and ln-5 gamma2-chain expression. The results also indicate that ln-5 gamma2-chain expression is upregulated during the progression of endometrial carcinoma.

Cell Adhesion Molecules↗

Classification of human ovarian tumors using multivariate data analysis of polypeptide expression patterns.

Large amounts of data on quantitative gene expression are generated by procedures such as 2-DE analysis of proteins or cDNA microarrays. Quantitative molecular variation may potentially be used for the development of methods for the classification of tumors. We used here the statistical concepts of principal components analysis (PCA) and partial least square analysis (PLS) in an attempt to type ovarian tumors. Using a set of 170 polypeptides, 22 tumors were used to establish a model ("learning set") for classification into 3 groups (benign/borderline/malignant). Eighteen tumors were then used to test the model. Six of 8 carcinomas and 3 of 4 borderline tumors were correctly classified. Two of 6 benign lesions were correctly classified, 3 were classified as borderline and 1 as carcinoma. We conclude that it may be possible to classify tumors according to their constitutive protein expression profile using multivariate analysis, thus making classification by artificial intelligence a future possibility.

Breast Neoplasms↗

Overestimated risk of second primary malignancies in ovarian cancer patients.

Registry-based cohort studies have established an increased risk of developing second primary malignancies (SPM) in patients with a primary ovarian cancer. In order to examine the accuracy of cancer registration with emphasis on registration of SPM, 344 women with ovarian cancer and 379 subsequent SPM, registered between 1958 and 1992 in the Stockholm-Gotland Cancer Registry (SGCR), a division of the Swedish Cancer Registry (SCR), were investigated. Complete records including pathology reports were examined and an additional histopathological evaluation was conducted for a sample of the group. The results revealed that 28 diagnoses of SPM were incorrectly registered (14 cases were misdiagnosed SPM of the gastrointestinal tract, mainly colon and rectum) and 34 women (with 38 SPM) were incorrectly registered with ovarian cancer. Recalculations of the risk of a subsequent cancer were performed on the basis of these findings and the results suggest an overestimation of the risk of developing SPM. Inferences of these findings to other primary sites of multiple malignancies should be made with caution and further studies are needed.

Cohort Studies↗

Recurrent fallopian tube carcinoma: TP53 mutation and clinical course.

Primary fallopian tube carcinoma is a rare, aggressive gynecological cancer; little is known about its cause. Previous studies have indicated that p53 immunopositivity is correlated with short-term survival in primary fallopian tube carcinoma. We examined p53 and p21/WAF1 immunostaining and TP53 mutation in exons 5 to 8 by single-stranded conformation polymorphism and constant denaturant gel electrophoresis in nine cases of primary fallopian tube carcinoma and their metastases/recurrences from patients who survived for between a few months and more than 20 years after diagnosis. We found that 1.) p53 immunopositivity without detectable p21/WAF1 immunostaining did not correlate with TP53 mutations in the conserved domains; 2.) mutations in TP53 occurred in two metastases/recurrences but not in their corresponding primary tumors; 3.) in two cancers, a TP53 mutation was observed in the primary tumor but not in the metastases/recurrences; 4.) constant denaturant gel electrophoresis seems to be more sensitive than single-stranded conformation polymorphism in detecting TP53 mutations; and 5.) in the nine cases studied, p53 immunoreactivity and/or TP53 mutation analysis did not correlate with tumor progression, survival, or response to treatment.

Aged↗

Recurrent primary pleomorphic adenomas of salivary gland origin: intrasurgical rupture, histopathologic features, and pseudopodia.

BACKGROUND: The rate of tumor recurrence after surgery for benign salivary gland pleomorphic adenoma varies considerably in different clinical settings and seems to depend to a great extent on the surgical technique used. The importance of tumor spillage for subsequent recurrence has recently been questioned. The current follow-up study was undertaken to ascertain whether intrasurgical rupture, tumor spillage, or any histopathologic feature might have had an impact on the rate of recurrence. METHODS: The medical records of all 255 patients operated on for benign salivary gland pleomorphic adenoma between the years 1974 and 1993 at the Department of Otorhinolaryngology, Huddinge University Hospital, were reviewed. All patients alive in April 1995 (n = 230) were sent a simple questionnaire. Two hundred thirteen of these patients received follow-up. All cases of tumor recurrence after surgery or intrasurgical rupture of the tumor capsule were reviewed histopathologically. RESULTS: Two (7.1%) of the 28 patients who had macroscopic capsule rupture during surgery experienced recurrence at a later stage. This was not a statistically higher rate than the 4.1% recurrence rate for the rest of the material. As many as 5 of the 9 primary tumors that subsequently recurred (56%) sent fingerlike tumor extensions or pseudopodia outside the pseudocapsule. The rate of occurrence of such structures was statistically higher than that of the tumors that ruptured during surgery (25%) and the examined uncomplicated cases (8%). CONCLUSIONS: Occurrence of pseudopodia--microscopic fingerlike formations of tumor tissue that extend beyond the main lump of the tumor--is a significant risk factor for local recurrence.

Adenoma, Pleomorphic↗

Primary carcinoma of the fallopian tube: comparative genomic hybridization reveals high genetic instability and a specific, recurring pattern of chromosomal aberrations.

Primary fallopian tube carcinoma (PFTC) is a rare and highly aggressive tumor. Twelve cases of PFTC (stages IA to IV) were analyzed by comparative genomic hybridization. The most consistent DNA gain was mapped to chromosome arm 3q in 11 of 12 cases. In six cases, the gain of 3q was present as a high level copy number increase (amplification) with a consensus region mapped to 3q26.2-qter. In the 12 cases, other frequent gains were located on chromosome arms 1q (in 11 cases), 2q (in 10), 7q (in 9), 8q (in 9), 5p (in 8), 6p (in 7), 12p (in 7), and 14q (in 6). Frequent copy number losses occurred on chromosome arms 16q (in 8 cases), 22q (in7), 6q (in 6). 8p (in 6), 18q (in 6), Xq (in 6), 1p (in 5), and 17p (in 5). All chromosomes were involved in chromosomal aberrations and the average number of copy alterations per case was 19.7. None of the 12 carcinomas revealed the presence of human papillomavirus (HPV) genomes. All of the cases exhibited crude aneuploidy. Strong p53 immunoreactivity could be observed in 10 of 12 cases while p21/WAF1 expression was low or undetectable. These results indicate that PFTC is a genomically highly unstable cancer, an observation that is in agreement with the poor prognosis associated with this tumor. A high frequency of 3q-gains has also been observed in HPV-related carcinomas of the uterine cervix. However, none of the PFTC was HPV related, suggesting that the 3q-gain is independent from HPV DNA.

Aged↗

Aggressive endometrial cancer in a young patient.

An unusually aggressive case of endometrial cancer in a 30 year old woman is presented. The patient experienced abnormal uterine bleeding, at times requiring blood transfusions, for almost half a year before the diagnosis was revealed. For obvious reasons there is a reluctancy to perform invasive examinations in young women. The diagnostic options are discussed.

Adenocarcinoma↗

The impact of tumour angiogenesis, p53 overexpression and proliferative activity (MIB-1) on survival in squamous cervical carcinoma.

Tumour angiogenesis (antifactor VIII-related antigen antibody), p53 overexpression (DO-1) and proliferative activity (MIB-1) were immunohistochemically analysed for the prediction of long-term survival in 113 patients with squamous cervical carcinoma. The median follow-up time was 82 months (range 72-99). In early stages (IB-IIA), neovascularisation was significantly related to tumour size. Significantly more patients in stage IIA had high tumour vascularity compared to stage IB (P < 0.01) but no significant difference was found between early and advanced stages (IIB-IVB) of cervical carcinoma. p53 overexpression was correlated to the stage of disease (P < 0.01). No relationship was found between tumour angiogenesis, p53 overexpression or MIB-1 and pelvic lymph node metastases, histological subtype or differentiation. Tumours with more than 50% p53 overexpression was significantly correlated with survival in the univariate analysis, but no independent predictive value was found. It is concluded that immunohistochemically detectable p53 overexpression as measured by DO-1 and proliferative activity as measured by MIB-1 seems of no clinical value for the prediction of long-term survival in squamous cervical carcinoma. The predictive value of tumour angiogenesis for survival outcome has still to be determined in squamous cervical carcinoma.

Adult↗

HPV-types, cytological and histopathological findings in three groups of women with possible HPV-related disease.

OBJECTIVE: The aim of this investigation was to study three groups of women presenting with possible HPV-infection with regard to HPV-types and cervical dysplasia. METHODS: Eighty women were included. Eighteen of them were present partners to men with condylomas, 20 had clinical vulvar HPV-lesions and 42 were referred due to an abnormal PAP-smear. Samples for HPV-analysis by PCR-technique were taken from the vulva, the portio and the cervical canal. A universal HPV-primer as well as specific primers for HPV 6/11, 16, 18, 31, and 33 were utilized. PAP-smears were taken as well as biopsies from cervix/portio. RESULTS: Seventy-eight percent had HPV-DNA identified. Sixty-seven percent of those with HPV 16 and/or 18 had dysplasia verified by histopathology and 50% of those with 31 and/or 33. Twenty of 21 women with dysplasia had HPV 16, 18, 31 and/or 33 identified. One woman with dysplasia was HPV-negative. Histopathologically verified CIN were diagnosed in all groups investigated. Women referred for suspicion of CIN significantly more often had HPV detected at the cervix/portio. HPV 6/11 was mostly found in women with condylomas. Apart from this the occurrence of the different HPV types were alike in the three groups. CONCLUSION: Infection with HPV is a process and the usefulness of different diagnostic methods seems to depend on when during the course of the disease they are used. HPV-findings in women with dysplasia were all associated with oncogenic virus-types. High-risk virus was often found simultaneously with low-risk virus indicating a covariation in the acquisition of the different HPV-types.

Adolescent↗

Biological malignancy grading in early-stage ovarian carcinoma.

The usefulness of adjuvant therapy in early ovarian cancer is a matter of controversy and there is a need for predictive methods to distinguish between low and high risk patients. Specimens from 95 early-stage ovarian cancer patients have been analysed for conventional clinical variables as well as for the biological markers--DNA content, MIB-1, p53, WAF-1--and correlated to survival. Prognostic significance achieved in univariate analysis could be improved by using a score based on several biological markers. Using a score based on DNA content, MIB-1, p53 and WAF-1, a significant predictor could be achieved with the aim of determining the postsurgical therapy. By using this tool, it is hoped that adjuvant therapy can be avoided for one-third of the patients with early-stage ovarian cancer.

Adult↗

Long-term adjuvant interferon treatment of human osteosarcoma. A pilot study.

During the period from 1971 to 1990 all osteosarcoma patients referred to the Karolinska Hospital without signs of metastases received human leukocyte interferon (IFN) as adjuvant treatment. Patients referred between 1985 and 1990 were given more intensive human leukocyte IFN treatment, i.e. a standard dose of 3 MU s.c. daily for 3-5 years. These 19 patients, all followed for 5 years, were included in a pilot study which entailed patients with central localization where radical surgery was not feasible. Metastases developed in 9 patients, of whom 3 had local recurrences. Sixty-three percent are free of disease at 5 years. Side-effects were negligible and long-term toxicity practically non-existent. It is suggested that a randomized multicenter IFN trial should be instituted on patients with poor prognosis receiving chemotherapy and/or that IFN treatment should be combined with other therapeutic modalities--irradiation, chemotherapy or anti-angiogenic substances--in osteosarcoma.

Bone Neoplasms↗

Decreased expression of Ras GTPase activating protein in human trophoblastic tumors.

The normally developing placenta undergoes extensive but regulated noninvasive cellular proliferation. Various proto-oncogenes and growth factors have been associated with the regulation of trophoblastic placental growth. Activation of some oncogenes and altered expression of growth factors have been demonstrated in trophoblastic tumors (hydatidiform mole and choriocarcinoma). The ras proto-oncogene plays a key role in the signal transduction cascade of activated growth factors, and is known to be activated or overexpressed in multiple tumor types. Ras GTPase activating protein (RasGAP), a major down-regulator of ras activity, is present at high levels in placenta. To assess the role that Ras-GAP plays in the development of trophoblastic tumors, we performed immunohistochemical analyses with anti RasGAP antibodies of normal placentas, hydatidiform moles, invasive moles, and malignant choriocarcinomas. Normal placentas and noninvasive hydatidiform mole displayed intense positive staining confined to trophoblasts, whereas no staining was observed in the trophoblasts of invasive moles or choriocarcinomas. Thus, there was an inverse correlation between expression levels of RasGAP protein and the invasive potential and malignant phenotype in human trophoblastic tumors. The data indicate that RasGAP may play a regulatory role in trophoblast proliferation and that abolishing its activity may be associated with malignant transformation of these cells.

Cell Transformation, Neoplastic↗

Prognostic value of amplification of c-erb-B2 in bladder carcinoma.

Amplification of c-erb-B2 is examined in patients with transitional cell bladder carcinoma. In a pilot study we found that the amplification correlated with high tumor grade. Tumor grade is a known prognostic factor. Therefore, we next examined the prognostic value of c-erb-B2 amplification in patients with >16 years of clinical follow-up. The gene copy number was determined, using semiquantitative PCR, in archival formalin-fixed tissues. Twenty-three percent (37/163 patients) showed the amplification. The amplification correlated with grade and stage. Moreover, we found that tumor grade (P < 0.001) and c-erb-B2 amplification (P < 0.001) showed prognostic information for survival. Patients with grade 3 tumors and concomitant c-erb-B2 amplification showed the worst prognosis. Multivariate analysis indicates that grade and c-erb-B2 amplification are independent prognostic factors.

Adult↗

Demonstration of gene-amplification by PCR in archival paraffin-embedded breast cancer tissue.

The polymerase chain reaction (PCR) is a powerful tool to examine genetic alterations in tumor samples. We describe a simple, rapid, nonisotopic PCR method to semi-quantitatively determine the number of gene copies in human formalin-fixed paraffin-embedded tissue. The procedure is exemplified by analysis of 15 years old breast cancer samples to determine the presence of amplification of c-erb-B2. The samples were obtained from routine specimens kept in pathological archives. Patients with amplified samples showed a poor prognosis, both for recurrences and death in breast cancer.

Archives↗

Combination of granulosa cell tumour and carcinoid in an imitation of appendix vermicularis within a mature teratoma--a unique case.

A case of primary carcinoid of the ovary in association with an imitation of appendix vermicularis is presented. These elements were thus parts of a mature teratoma. In the other ovary a granulosa cell tumour with a similar morphology was found. Following surgery no additional treatment was administered and the patient is well 13 years after the diagnosis.

Aged↗