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| 2. |
- Arnerlöv, Conny, 1952-
(författare)
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Prediction of prognosis in human breast cancer : a study on clinicopathologic and cytometric prognostic factors
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study was undertaken to evaluate some important prognostic factors in human breast cancer. The prognostic value of accepted clinicopathological factors such as the presence of axillary lymph node métastasés, histologic grade, clinical and pathological stage was confirmed.In a cohort of stage T3,T4,M0 breast cancer with 91 patients (paper I) DNA ploidy by static cytometry (SCM) turned out to be the most important prognostic factor. In a cohort of stage T2,M0 breast cancer with 99 patients (paper III) the presence of involved axillary nodes and low histologic grade were independent prognostic factors. According to life-table analyses DNA ploidy by flow cytometty (FCM) and SCM were significant prognostic predictors for survival but S-phase fraction (SPF) was not. The significant discrimination between euploid and aneuploid tumours was seen also among the node-negative patients. In a patient material with 158 tumours of predominantly low stages (73% T0,T1, papers IV and V) and calculated mammographie tumour volume doubling time (DT) DNA ploidy by FCM gave no significant prognostic information. A computer program was used to calculate SPF from the histograms obtained by FCM. SPF with a cut-off value of 7.5% between tumours with high and low proliferation rate was a highly significant and independent prognostic factor for survival. The other independent prognostic predictors were low histologic grade, the presence of involved axillary nodes and stage II and III (versus stage I).DT values for 158 patients (papers IV and V) varied between 0.6 and 65.8 months (mean 10.9 months) and 11 tumours showed no growth at all between mammographies. The median value of 9.0 months was chosen as cut-off point between slow and fast growing tumours. The prognostic power of DT was however low, and the difference between slow and fast growing tumours was significant only for distant disease-free survival. Seventy-one of the 158 tumours were detected by mammographie screening. The screening detected carcinomas with predominantly long DT:s were discovered at an early stage and showed favourable characteristics concerning DNA ploidy and SPF.FCM was a rapid and reliable method for DNA analysis with a better prognostic discrimination between euploid and aneuploid groups than SCM (papers II and III).SPF, DNA ploidy and histologic grade are significantly correlated to one another but show no strong correlation to the presence of axillary lymph node métastasés. There is also a significant correlation between DT on one hand and DNA ploidy and SPF on the other hand.In conclusion the classic prognostic factors are still valuable. DNA ploidy as a single prognostic factor seems to have a relatively low prognostic power and seems to be of limited clinical value. SPF is a highly significant prognostic predictor for breast cancer of low stage, but the clinical value is not defined.
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- Augustsson, A, et al.
(författare)
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Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population.
- 1991
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 71:6, s. 518-24
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Tidskriftsartikel (refereegranskat)abstract
- Common naevi, dysplastic naevi (DN) and other phenotypic features were evaluated as melanoma risk factors in a Swedish case-control study. One-hundred and twenty-one prevalent melanoma cases and 378 randomly selected controls participated. The mean total body naevus count was 115 in the cases and 67 in the controls. Fifty-six per cent of the cases and 18% of the controls had clinical DN. The corresponding figures for histologically diagnosed DN were 40% and 8% respectively. Clinical DN was as good as histologically diagnosed DN in identifying individuals at risk for melanoma. Subjects with sun-sensitive skin, greater than or equal to 150 naevi and presence of DN have 50 times higher melanoma risk than those without these characteristics.
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| 4. |
- Augustsson, A, et al.
(författare)
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Melanocytic naevi in sun-exposed and protected skin in melanoma patients and controls.
- 1991
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 71:6, s. 512-7
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Tidskriftsartikel (refereegranskat)abstract
- The possible link between exposure to ultraviolet light and naevus development was studied in 121 melanoma patients and 310 controls by comparing the number of naevi in a sun-exposed area on the back with that in a sun-protected area on the buttocks. Both patients and controls had a four-fold increase in the number of naevi in the exposed compared with the protected area, p less than 0.001. The difference in naevus count between the exposed and the protected area was larger in patients than in controls, p less than 0.001. Subjects with dysplastic naevi, melanoma patients as well as controls, had a larger difference in the number of naevi between the two areas than subjects without dysplastic naevi, p less than 0.001. These results support the idea that sunlight plays an important role in naevus development and may explain why a high naevus count is a risk marker for malignant melanoma.
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| 5. |
- Augustsson, A, et al.
(författare)
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Prevalence of common and dysplastic naevi in a Swedish population.
- 1991
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Ingår i: The British journal of dermatology. - 0007-0963. ; 124:2, s. 152-6
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Tidskriftsartikel (refereegranskat)abstract
- The naevus profile was examined in a Swedish population that was randomly selected from a census file. The participation rate was considered high at 82%. The number of common naevi (CN) and the prevalence of dysplastic naevi (DN) were investigated in 379 subjects (aged 30-50 years). The mean total body count of CN greater than or equal to 2 mm was 67 (range 1-300). As many as 22% of the population had 100 naevi or more and only 18% had less than 25. The counts were not influenced by age or sex. DN were diagnosed clinically in 18% (CI 14-22%) of the subjects and histologically in 8% (CI 5-11%). Subjects with dysplastic naevi had a significantly larger number of common naevi and a more sun-sensitive skin type than subjects without DN, P less than 0.001.
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| 7. |
- Borg, A., et al.
(författare)
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Association of int2/hst1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis
- 1991
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 63:1, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in proviral induced mammary carcinoma) has been mapped to chromosome llql3 and found to share band localisation with, among others, the HST1 proto-oncogene. Both genes are members of the fibroblast growth factor family. In the present study, coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311 invasive human breast carcinomas using slot blot and Southern blot analyses. Amplification was not correlated to tumour size, axillary lymph node status or stage of disease, neither to patient age nor menopausal status. However, 26 (96%) of the 27 amplified tumours were, often strongly, Oestrogen receptor positive compared to 65% of the unamplified cases (P = 0. 001). These findings are in sharp contrast to the strong correlations of HER-2/neu proto-oncogene amplification with advanced stage and steroid receptor negativity, previously observed in the same series of tumours. Patients with INT2/HSTI amplified breast cancer had a significantly shorter disease-free survival compared to those with unamplified genes (P = 0. 015, median follow up 45 months). This correlation was confined to node-negative patients and persisted in multivariate analysis. No significant correlation to survival from breast cancer was found. It is concluded that amplification of the 1 lql3 region in breast cancer occurs in a particular subset of aggressive tumours, quite different from that identified by HER-2/neu amplification. It still remains to be shown that the selection for amplified genes at llql3 is due to the activity of INT2, HSTl or yet another, still unidentified, neighbouring gene. However, the results are potentially of clinical value in separating a group of node-negative breast cancer for more intense treatment.
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| 8. |
- Borg, Åke, et al.
(författare)
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ERBB2 amplification in breast cancer with a high rate of proliferation
- 1991
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Ingår i: Oncogene. - 1476-5594. ; 6:1, s. 137-143
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Tidskriftsartikel (refereegranskat)abstract
- The ERBB2 proto-oncogene was studied in 539 invasive primary breast tumors and was found amplified (2- greater than 30 copies) in 19%. Amplification was correlated to most known risk factors, including; large tumor size, lymph node positivity and many tumor involved nodes, advanced stage, low patient age (less than 40 years), non-diploidy and hypertetraploidy, and most significantly (P less than 0.00001) to the absence of steroid receptors and to a high rate of proliferation (flow cytometric determined S phase fraction). ERBB2 amplification was strongly associated (P less than 0.0001) with early recurrence and death in breast cancer among node-positive patients. This connection did not, however, remain in multivariate analyses. No correlations to clinical outcome were seen among node-negative patients. Similarly, non-diploid, but not diploid, amplified tumors were particularly aggressive. Furthermore, ERBB2 amplification was associated with a high rate of proliferation and poor prognosis in steroid receptor positive, but not receptor negative tumors. In progesterone receptor positive breast cancer, amplification was an independent and with node status equally powerful (P less than 0.0001) predictor of poor survival. It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability. Its clinical relevance as a prognostic factor may be in selecting a high risk subgroup of breast cancer, in general considered as being of good prognosis.
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| 9. |
- Dictor, Michael, et al.
(författare)
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Flow cytometric DNA content in Kaposi's sarcoma by histologic stage. Comparison with angiosarcoma
- 1991
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Ingår i: Analytical and Quantitative Cytology and Histology. - 0884-6812. ; 13:3, s. 201-208
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Tidskriftsartikel (refereegranskat)abstract
- Kaposi's sarcoma occurs as a multicentric proliferation of endothelial cells. A lesion may progress through several histologic stages, culminating in a lesion consisting of spindle cells with marked nuclear atypia that may be indistinguishable from angiosarcoma. To assess the relationship between the nuclear DNA content and the stage, 29 paraffin-embedded biopsy specimens from 25 cases of Kaposi's sarcoma were classified according to their histologic stage and flow cytometric DNA ploidy status. The findings were compared with those in 14 angiosarcomas (5 postmastectomy angiosarcomas, 6 other cutaneous angiosarcomas and 3 angiosarcomas of deep tissues). The Kaposi's sarcoma specimens studied included samples with irregular lymphatic-like channels (stage 1), transition to spindle cells (stage 1t2), nodular spindle-cell aggregates (stage 2), scattered atypical spindle cells (stage 2t3) and histologic features indistinguishable from those of angiosarcoma (stage 3). Of the 25 Kaposi's sarcoma specimens of stage 2 or less, 17 had a diploid DNA distribution while an additional 8 had broad diploid G0G1 peaks (peridiploid, with a coefficient of variation greater than 7.5%, present in similar proportions in stages 1, 1t2 and 2). One of three stage 2t3 lesions showed tetraploidy while the single stage 3 specimen (from the leg) was aneuploid, with a DNA index (DI = 1.16) similar to that of four of the five postmastectomy angiosarcomas (DI = 1.14 to 1.20). An additional three angiosarcomas also showed nondiploid distributions (DI = 1.16, 1.98 and 2.13, respectively); the remainder were diploid or peridiploid. These results support previous cytogenetic data suggesting a normal karyotype in Kaposi's sarcoma up to stage 2, with atypia beginning as cells acquire numerical and structural chromosomal aberrations.
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| 10. |
- Evander, Magnus, 1959-
(författare)
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Detection of human papillomavirus : a study of normal cells, cervical intraepithelial neoplasia and cancer of the uterine cervix
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human papillomavirus (HPV) infections of the genital tract are now recognized to be among the most prevalent sexually transmitted diseases and also a contributing factor to some cancers of the lower genital tract of women and men. Presence of HPV in a clinical specimen is confined to detection of the HPV genome by DNA hybridization techniques.In this thesis, the commonly used DNA hybridization techniques Southern blot and filter in situ hybridization (FISH), were first used for detection of genital HPV infection. In order to increase and simplify the detection of HPV in clinical specimens a more sensitive technique, the polymerase chain reaction (PCR) was subsequently utilized.For type-specific amplificaiton of HPV 6, 16, 18 and 33 by PCR, oligonucleotide primers located in the E6 and E7 regions of the HPV genome were selected. They were found to specifically amplify the four types. To be able to amplify a broad spectrum of genital HPV types, general primers located in the E7 and El region of the HPV genome, were designed and evaluated. They were found to amplify a wide range of genital HPV types. To further increase the sensitivity and specificity, a two-step PCR using general primers, was assembled and evaluated against a one-step PCR on cervical scrapes from young women in a population-based study. The two-step PCR increased the sensitivity about three-fold compared to the one-step PCR.By Southern blot and FISH, 46% of women with abnormal Papanicolaou (Pap) smears were shown to carry HPV DNA. Of the women analysed by Southern blot, 39 % harboured HPV DNA and 25 % proved HPV 16 positive. Of the samples analysed with FISH, 27 % contained HPV DNA, compared to 11 % of samples from a group of reference women with normal cytology. With the Southern blot technique, HPV DNA was detected in 66% of women with cervical intraepithelial neoplasia grade III (CIN III) lesions. Fifty-four percent of the women with CIN III lesions were positive for HPV 16 DNA.By type-specific PCR, 12 out of 13 women with cervical squamous carcinoma were shown to carry HPV 16 and/or 18. Among women with adenosquamous carcinoma of the cervix, HPV 18 was the most prevalent type (26%) but HPV 16 was also found in a proportion of the women(15 %). Nine of 13 premenopausal cases with cervical adenocarcinoma were HPV positive compared to only 2 of 13 postmenopausal cases (p< 0.015). HPV 16 DNA was detected in 48%of women with cervical intraepithelial neoplasia (CIN), by the use of type-specific PCR.Three different groups of women with normal cytology were studied. Among women attending a family planning clinic in Kenya, 19% were shown to carry HPV virus, by the use of general primers. HPV 16 was found in 5.2% of these women and HPV 18 in 3.9%. In anothergroup of women, attending the gynecological department in Umeå, HPV 16 DNA was detected in 21 % by type-specific PCR. However, if consideration was taken to the medical status of the women, only 10% of women without any medical history were HPV 16 DNA positive, versus 54% of women with diseases and women with a relative progesterone dominance. Finally, by use of a two-step PCR using general primers, 20% of young women from Umeå taking part in a population-based study were demonstrated to carry HPV DNA. The most prevalent types were HPV 6 (2.0%) and HPV 16(2.7%). Among the women in this study with normal cytology, 19%were HPV positive.
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