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Background: All patients with medullary carcinoma of the thyroid (MCT) diagnosed in Sweden during 1959 through 1981 were identified. There were 113 males and 134 females with a mean age of 51.6 years (range, 11-85 years). The cohort was followed with regard to survival to identify prognostic factors. The results 5 and 10 years after diagnosis have been presented previously., Methods: The purpose of this study was to examine to what extent those prognostic factors found in the authors' previous analyses remained independent prognostic factors for survival 10 years or longer after diagnosis. The follow-up period was extended an additional 5 years and ranged between 11 and 32 years., Results: The relative survival rate was 69.2% and 64.7%, respectively, 10 and 15 years after diagnosis. The survival rate was worse after excluding those patients with a family history of MCT (60.8% and 53.7%, respectively, 10 and 15 years after diagnosis). In multivariate analyses, age, tumor size, stage of the disease at diagnosis, tumor amyloid content and an euploid DNA pattern were found to be independent prognostic factors. However, in analyses of survival 10 years or longer after diagnosis only stage, tumor size, and age remained independent prognostic factors., Conclusions: There is still an excess mortality 10 years or longer after a diagnosis of MCT. However, the authors identified 3 groups of patients in whom the survival 10 years or longer after diagnosis did not differ from that of the general population: patients with a family history of MCT detected by screening, those with tumor size < 1 cm, or those with early stage disease at diagnosis.

Background: The understanding of proliferation is a central issue in oncology. Several methods exist for the assessment of the growth fraction and cell-cycle time, but comparative studies that give the clinician advice about the most reliable use of new markers are few. The aim of the current study was to perform methodologic, descriptive, comparative, and prognostic studies of Ki-67, proliferating cell nuclear antigen (PCNA), and flow cytometric S-phase fraction (SPF) in endometrial carcinoma., Methods: The expression of Ki 67 (n = 175) and PCNA (n = 146) were studied immunohistochemically; and the SPF (n = 297) by flow cytometry. The median follow-up time was 78 months., Results: Neither Ki-67 nor PCNA had any correlation to either the stage or the histopathologic subtype of the tumors, but they were covariant with the histopathologic grade (P < 0.05). There was an interrelationship between Ki-67 and PCNA (P < 0.001), and both were associated with the size of the SPF (P < 0.0001 and P < 0.05, respectively). Mean SPF was high in advanced stages and strongly associated with histopathologic subtype (P < 0.0001) and ploidy (P < 0.0001). Tumors with strong Ki-67 expression were more often aneuploid (P < 0.01). In initial analyses, Ki-67 and SPF were predictors of poor survival (P < 0.05 and P < 0.001, respectively), whereas PCNA was not. When SPF was added to a comprehensive multivariate model, Ki-67 provided no further prognostic information, whereas SPF remained a powerful predictor of survival., Conclusions: Ki-67 and, to a lesser extent, PCNA, give approximate estimates of the growth fraction, whereas SPF only reflects the proportion of cells in S-phase. However, SPF is by far the strongest predictor of survival.

Background: Cytologic screening can reduce mortality from cervical cancer by detection and removal of premalignant lesions. Conceivably, mortality is further reduced because more women with invasive disease are diagnosed at an earlier, curable stage. This hypothesis can be assessed in Sweden, where population-based screening programs were introduced successively over about a decade starting in 1964., Methods: Record linkages permitted complete follow-up through 1986 of all 17,377 patients with invasive cervical cancer diagnosed in Sweden from 1960 through 1984. We analyzed relative survival rates that describe the survival of patients after elimination of the effects of causes of death other than cancer of the cervix., Results: Prognosis improved substantially in patients younger than age 50 years at diagnosis; from 1960-1964 to 1980-1984, the 5-year relative survival rate increased from 69.8% to 88.8% at age 20-29 years, from 71.7% to 85.5% at age 30-39 years, and from 68.6% to 77.9% at age 40-49 years. The excess mortality was thus reduced by more than half in patients diagnosed when younger than 40 years. In contrast, only slight or no improvement was noted in those diagnosed at older ages when screening was less extensive. In all time periods, a strong association was found between older age at diagnosis and poorer prognosis., Conclusion: Although alternative explanations for our findings must be seriously considered, the most obvious interpretation is that cytologic screening reduces mortality from cervical cancer by earlier diagnosis of invasive disease.

Background: The natural history of prostatic cancer is variable. Our knowledge of prognostic factors is limited; therefore, research is needed., Methods: The cases of 300 population-based consecutive patients with a diagnosis of cancer of the prostate were analyzed regarding different prognostic factors (but with special reference to the erythrocyte sedimentation rate [ESR])., Results: After a mean observation time of 100 months, M category, ESR, grade, performance status, hemoglobin level, and T category were found to correlate with disease-specific death using multivariate analysis. The variables correlating with progression in the multivariate model were M category, ESR, T category, grade, treatment, and age. Patients treated with estrogen had a significantly lower risk (relative hazard, 0.3) of relapse. ESR was highly statistically significant (P less than 0.0001) as a prognostic factor. With the variable in linear form, a 20-mm/h higher level suggested a 29% increased risk, on average, for dying of prostatic cancer (using a best-fit multivariate model). However, the relationship was not linear. After correcting for the effect of other factors, the risk for dying of prostatic cancer was lowest when the ESR was 40-50 mm/h and highest when its values were highest., Conclusions: ESR is an indicator of increased risk of progression and death in prostatic cancer. Other prognostic factors such as M and T categories, grade, performance status, hemoglobin level, and age currently are more important when planning treatment. It is possible that the ESR reflects aspects of tumor-host relationship and that both a low and high ESR are markers for patients with receding host defence mechanism.

In a nationwide study of medullary thyroid carcinoma, the relation between nuclear DNA content and survival was studied in 211 patients with complete follow-up of up to 27 years. Morphologically identified tumor cells were analyzed by an image cytometric method. The DNA histograms were classified (1) by an objective method in which the degree of aneuploidy was defined as the percentage number of tumor cells with DNA values exceeding the 90th percentile of diploid control cells (P90), and (2) according to a subjective evaluation of whether the DNA profiles represented a euploid or an aneuploid DNA pattern. Both classifications separated groups with marked differences (P less than 0.001) in survival. A multivariate proportional hazards analysis indicated that each method provided additional information when the other one was taken into account. In patients whose tumors were classified according to the objective P90 method 1, the relative hazards (with 95% confidence interval) in the groups with P90 values of 36% to 69% and greater than or equal to 70% were 1.6 (0.9-2.8) and 2.1 (1.1-4.0) respectively, compared with the reference group. With the subjective method 2 the corresponding figure for the group with aneuploid tumors was 1.7 (1.0-2.0) compared with the group with euploid tumors.

All patients with medullary thyroid carcinoma (MTC) diagnosed in Sweden during 1959 through 1981 were recruited for study from the Swedish Cancer Registry. Among a total of 249 patients, 66 were diagnosed in 1959 through 1969 and 183 from 1970 through 1981. Apparently sporadic MTC was present in 186 patients, and familial MTC in 63. Twenty-seven patients with familial MTC were diagnosed from clinical symptoms and 36 by screening. In both the sporadic group and the symptomatic familial group, approximately 80% of the patients had palpable thyroid tumors. Lymph node metastases were present in 44% of the sporadic group and in 37% of the group with symptomatic familial MTC, and distant metastases in approximately 20% of the patients in each of these groups. The patients detected by screening differed significantly from the two groups of symptomatic cases by having a lower frequency of palpable thyroid lesions (50%), smaller tumors, and lower frequencies of cervical lymph node metastases (14%) and distant metastases (0%). Multivariate analyses revealed no significant differences between sporadic cases and symptomatic familial cases regarding tumor size or stage. Large tumors (greater than 3 cm) were more frequently accompanied by palpable cervical lymph nodes and were associated with an approximately four times higher risk of distant metastases than tumors smaller than 1 cm. Women had significantly smaller tumors and a more favorable stage distribution than age-related men.

This epidemiologic investigation comprised 1351 of 1423 women in a defined geographic area consecutively diagnosed as having a primary breast cancer. Simultaneous bilateral disease occurred in only 1 patient, whereas a history of previous cancer in the contralateral breast was reported by 65 patients. This prevalence was related to that of 23 previous cases in an age-matched control group of 1351 women from the same population. The relative risk of developing a second primary was 2.9 (95% confidence limit, 1.8-4.6) for the whole material and remained seemingly constant over several decades at a level predetermined by age at first diagnosis, namely 9.9 (95% confidence limit, 3.8-25.8) before the age of 50 and 1.9 (95% confidence limit, 1.1-3.2) after that age. The incidence ratio of bilateral to unilateral disease was used as an estimate of the lifetime risk of developing a second primary in this stable and well-defined population. This calculation revealed cumulative risk figures of 13.3% and 3.5% for women younger and older than 50 years, respectively, at first diagnosis. It was concluded that the occurrence of bilateral disease, which reflects a multicentric neoplastic transformation of the breast epithelium, is a characteristic of early-occurring (premenopausal) disease.

Complete follow-up for 4 to 27 years was achieved for virtually all 249 patients with medullary thyroid carcinoma (MTC) diagnosed in Sweden in a 23-year period. Tumor specimens from 241 patients were re-examined with regard to calcitonin immunoreactivity, amyloid content, argyrophil reaction, tumor capsule condition, and nuclear DNA content. In univariate analyses, these factors, with the exception of the argyrophil reaction, were strong predictors of survival. There were twofold-to-threefold differences in hazard rate between patients with a high (greater than 50%) and low (less than 10%) frequency of calcitonin-immunoreactive tumor cells, between those with amyloid-containing and amyloid-free tumors, and between those with an intact and a nonintact tumor capsule. Calcitonin immunoreactivity and the amyloid content also provided prognostic information in multivariate analyses that adjusted for all the other factors mentioned above and in the full multivariate model, which in addition considered age, sex, heredity, stage of the disease, tumor size, and treatment. The strong prognostic capacity of the nuclear DNA content found in univariate analyses became considerably weaker when other morphologic characteristics were considered.