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P Lipponen

Publications and source records attributed to P Lipponen.

At least 91 records · Page 5Linked to original sources

Prognostic factors after 5 years follow-up in female breast cancer.

A consecutive series of breast carcinomas (n = 595) followed up for a minimum of 7.5 years was analyzed for clinical, histological and morphometric prognostic factors after 5-years' follow-up. Tumor size, nodal status, mitotic frequency and patients' age at diagnosis predicted survival at 7.5 years highly significantly (p less than 0.0001). Tubule formation (p = 0.002), histological grade (p = 0.026) and nuclear pleomorphism (p = 0.046) were related to prognosis as well. In N--patients mitotic frequency (p = 0.018) was the best predictor of survival at 7.5 years whereas in N + tumors tumor size (p = 0.0013), tubule formation (p = 0.003) and mitotic frequency (p = 0.0049) were the best predictors of survival at 7.5 years. In univariate survival analysis the age of the patients (p = 0.002), tubule formation (p = 0.005), axillary lymph node status (p = 0.008), lymphocyte infiltration (p = 0.049), mitotic frequency (p = 0.06) and tumor size (p = 0.08) predicted survival after 5 years' follow-up. Tubule formation predicted survival (p = 0.025) in N - patients and in N + tumors the age of the patients was the most important predictor (p = 0.006). In Cox's analysis tubule formation (p = 0.13), axillary lymph node status (p = 0.033), SD of nuclear perimetry (p = 0.046) and intraductal growth (p = 0.059) predicted survival independently after 5 years' follow-up.

Age Factors↗

DNA ploidy, S-phase fraction, and G2 fraction as prognostic determinants in human pancreatic cancer.

The DNA ploidy, S-phase fraction (SPF), and G2 fraction of pancreatic cancer tissue was measured by flow cytometry in 95 patients. Forty-nine per cent (n = 47) had a diploid DNA index, and 51% (n = 48) of tumours were aneuploid. Aneuploid tumours and high-grade tumours had significantly higher S-phase and G2-fraction values than diploid tumours or low-grade tumours. Diploid and tetraploid tumours had a more favourable prognosis than non-tetraploid aneuploid tumours (p = 0.0020) during the mean follow-up of 6 years. The type of therapy (p = 0.07), histologic grade (p = 0.06), SPF (p = 0.1), and G2 fraction (p = 0.02) had predictive value in survival analysis as well. In multivariate survival analysis, including flow-cytometric, histologic, and clinical variables, diploidy and tetraploidy had independent predictive value. The results suggest that flow cytometry might be used in grading of pancreatic cancer. Such a grading would have practical value if new modes of therapy are being developed. Forty-one per cent of multiple samples had a heterogeneous DNA index when multiple samples were used. Consequently, flow cytometric analysis of pancreatic cancer using multiple samples is recommended.

Adenocarcinoma↗

Demographic prognostic factors in breast cancer.

The aim of this study was to assess the prognostic influence of the month of treatment, the year of treatment, and the patient's age at diagnosis of breast cancer in comparison with clinical and histopathological prognostic factors. This retrospective analysis from the years 1968-1990 at one university hospital in a rural area in Eastern Finland included 688 patients with invasive breast cancer followed up for more than 12 years. The breast tumours diagnosed in September and in October were larger, had distant metastases more often and, accordingly, had a worse prognosis than the tumours diagnosed during the rest of the year. The prognosis of breast tumours improved during the study period whereas the patient's age was inversely related to prognosis. The histopathological characteristics of breast tumours were not related to the month of treatment. The tumours were histologically more atypical and smaller in size, and the patients were older at diagnosis in the 1990's than in the 1980's. In conclusion, the month of treatment, the year of treatment, and the patient's age were found to be independent prognostic predictors in breast cancer, acting as confounders in survival analyses based on the biological prognostic factors.

Age Factors↗

A review of prognostic factors in human pancreatic adenocarcinoma.

The incidence of pancreatic adenocarcinoma is increasing. Pancreatic cancer generally grows without early symptoms until late in its natural history and thus presents many discouraging unresolved problems in management. This review analyses the present state of improved histoquantitative techniques for prognostic assessment of pancreatic cancer. Nuclear morphometry analysis of mitotic rate and DNA flow cytometry can efficiently grade pancreatic cancer into groups with distinctly different prognoses. The practical value of quantitative grading in pancreatic adenocarcinoma today is, however, limited. Efficient grading may have greater clinical relevance after future developments of therapeutic modalities for pancreatic adenocarcinoma.

Adenocarcinoma↗

Prediction of outcome after first recurrence of breast cancer.

OBJECTIVE: To assess the independent power of certain clinical, histological, and morphometric variables to predict survival after first recurrence of breast cancer. DESIGN: Long term follow up study. SETTING: Departments of surgery and pathology, University Hospital. SUBJECTS: 212 patients (from a consecutive series of 517) who developed recurrence after primary treatment of breast cancer between 1968 and 1990. INTERVENTIONS: Re-examination of histology of primary tumours, follow up of patients, and calculation of predictive score by Cox's regression analysis. RESULTS: The nodal status at the time of diagnosis (p less than 0.001), the SD of the nuclear area (p = 0.01), the degree of tubule formation (p = 0.003), and the age of patient, were all independent predictors. The most important predictor of survival was the prognostic score derived from the coefficients of the Cox's model (p less than 0.0001). CONCLUSION: Survival after first recurrence can be accurately predicted by advanced histological analysis of the primary tumour tissue. Combination of independent predictors permits even more accurate estimation of survival time.

Breast↗

Nuclear morphometry and DNA flow cytometry as prognostic factors in female breast cancer.

OBJECTIVE: To evaluate the predictive value of traditional prognostic factors, nuclear morphometry, and flow cytometric data in invasive breast cancer. DESIGN: Open study. SETTING: One university hospital in Finland. SUBJECTS: 248 women with invasive breast cancer followed up for more than 11 years. MAIN OUTCOME MEASURES: Univariate and multivariate analysis of factors thought to indicate prognosis. RESULTS: Diameter of the tumour, lymph node status, S phase fraction. DNA index, the age of the patient, and the SD of nuclear perimeter were significant independent predictors in the whole series in a multivariate analysis. In node negative patients the SED of the nuclear perimeter and diameter of the tumour had independent prognostic value, whereas in node positive patients diameter of the tumour and the S phase fraction were independently related to survival. CONCLUSIONS: Diameter of the tumour is an important prognostic factor in breast carcinomas. Histoquantitative methods are superior to conventional histological techniques for the prediction of outcome in women with breast cancer.

Adult↗

Prognostic scores combining clinical, histological and morphometric variables in assessment of the disease outcome in female breast cancer.

Clinical features, 8 histological features, 7 nuclear morphometric variables and 2 mitotic indices were entered in a Cox's model to assess their independent predictive power in a series of 517 breast cancer patients followed up for over 10 years. The volume-corrected mitotic index (M/V index) (p less than 0.001), axillary lymph-node status (p = 0.002), the shortest nuclear axis (p = 0.006) and the degree of tubule formation (p = 0.02) predicted independently the recurrence-free survival. In N- tumours (n = 293), the M/V index (p = 0.005), the degree of tubule formation (p = 0.016) and tumour size (p = 0.023) were independent prognostic predictors, whereas in N+ tumours (n = 224), only the M/V index (p = 0.004) and the maximum nuclear axis (p = 0.004) had independent prognostic value. The corrected survival was predicted independently by the axillary lymph-node status, degree of tubule formation, M/V index, tumour size (p less than 0.001), age (p = 0.002) and year of treatment (p = 0.008). In N- tumours, the degree of tubule formation (p = 0.005) and intraductal growth pattern (p = 0.015) exhibited independent predictive value. In N+ tumours, patient survival was related to the M/V index (p less than 0.001), tumour size (p = 0.005) and patient age (p = 0.005). The results show that the assessment of the M/V index, axillary lymph-node status, tumour size, intraductal growth pattern and tubule formation are reliable factors in predicting the prognosis of breast cancer. The conventional mitotic activity index (MAI) and histological grading should be replaced by the M/V index in histological assessment of malignancy in breast cancer. The prognostic scores combining the independent variables reflecting the proliferative rate and metastatic potential of the tumours are more accurate predictors of the recurrence-free survival and overall survival (p less than 0.0001) than the single variables used alone.

Breast Neoplasms↗

Prognostic factors in axillary lymph node-negative (pN-) breast carcinomas.

Axillary lymph node-negative (pN-) breast carcinomas (n = 281) were analysed histoquantitatively for two mitotic indexes (MAI, mitotic activity index; M/V, volume corrected mitotic index) and nine nuclear factors with special emphasis on disclosing prognostic factors during a follow-up of 12 years. The M/V index (P = 0.0018), tumour size (P = 0.0052), MAI (P = 0.0115) and histological grade (P = 0.0565) predicted the recurrence-free survival. MAI (P = 0.0007), M/V index (P = 0.0046), tumour size (P = 0.0133), histological grade (P = 0.0528) and S.D. of the nuclear perimetry (P = 0.07) predicted the disease-related survival. In Cox's analysis, MAI (P = 0.004), adjuvant therapy (P = 0.03) and tumour size (P = 0.09) predicted survival independently. Recurrence-free survival was related independently to nuclear perimetry (P less than 0.001), SD of nuclear area (P = 0.01) and MAI (P = 0.019) in Cox's analysis. In small (diameter less than or equal to 20 mm) tumours, S.D. of nuclear perimetry predicted recurrence-free survival (P = 0.03) in Cox's analysis. The results advocate the use of mitotic indexes and nuclear factors in place or in combination with conventional histological grading in predicting the survival and tumour recurrence in axillary lymph node-negative breast carcinomas.

Breast Neoplasms↗

Relationship between DNA ploidy and survival in patients with exocrine pancreatic cancer.

The DNA ploidy of pancreatic cancer tissue from paraffin blocks was measured by flow cytometry in 46 patients whose disease had been detected and treated with surgery. Lymph node involvement was observed at the time of diagnosis in 36% of patients with diploid tumors and in 79% of patients with aneuploid tumors (p = 0.017), but no clear relation to metastasis could be observed (p = 0.201). The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumors (p = 0.007). All patients who underwent radical surgery had diploid DNA content and SPF below the median (11.5%). Seven patients with a diploid tumor (32%) and none of the aneuploid cases survived 1 year. Over the 1-year period, in order of importance, the type of treatment (p less than 0.001), DNA ploidy (p = 0.004), tumor size (p = 0.0046), and lymph node status (p = 0.027) predicted survival. Aneuploidy showed a significant association with decreased cumulative survival (p = 0.015), and a suggestive relationship with SPF was found. The results suggest that DNA ploidy of pancreatic cancer can be used in dividing the patients into different prognostic groups. The value of the detection of aneuploidy, however, is limited, because diploid pancreatic cancers are also generally rapidly fatal.

Adult↗

DNA ploidy, S phase fraction and G2 fraction as prognostic determinants in prostatic adenocarcinoma.

The results of DNA flow cytometry (FCM), histological features and clinical stage of prostatic adenocarcinoma were correlated to outcome in 91 patients during a mean follow-up period of 15.6 years. Aneuploidy was detected in 33 (36%) tumours, and 59 (64%) tumours were diploid. Eighteen (20%) tumours showed a tetraploid DNA index. The frequency of tetraploidy increased towards high-stage and high-grade tumours. Aneuploidy, high S phase fraction (SPF) and G2 fraction were significantly related to clinical stage, histological grade and perineural infiltration. Progressing tumours (T category) had higher SPF values (p = 0.0248), and progression in N (p = 0.0122) and M categories (p = 0.0021) was related to high G2 fraction as well. In T1-2 tumours, DNA ploidy (p = 0.0280) and SPF (p = 0.0230) predicted progression, whereas histological grade had no significant predictive value. The clinical stage (T) predicted crude survival (p = 0.0005). Results show that FCM gives prognostic information in prostatic adenocarcinoma beyond that of histological grading.

Adenocarcinoma↗

Use of immunohistochemically demonstrated c-erb B-2 oncoprotein expression as a prognostic factor in transitional cell carcinoma of the urinary bladder.

Formalin-fixed, paraffin-embedded specimens from 91 primary transitional cell cancers (TCC) of the urinary bladder were stained with a monoclonal antibody to c-erb B-2 oncoprotein. Twelve percent (11/91) of the TCC stained for c-erb b-2 oncoprotein, and in 4% (4/91) of cases, the expression was graded as moderate or heavy. The expression of c-erb B-2 was significantly (p = 0.072) related to the WHO grade, whereas no significant difference in its expression was found between (a) the superficial and invasive TCC and (b) between the papillary and nonpapillary TCC. One of the tumours had a verified metastasis at the time of diagnosis and it exhibited heavy expression of c-erb B-2. The expression of c-erb B-2 was significantly related to the number of nucleolar organiser regions/TCC nucleus (p = 0.003). Aneuploid TCC were more frequently associated with moderate or heavy expression of c-erb B-2 than the diploid ones. Recurrence and progression of TCC could not be significantly related to expression of c-erb B-2 oncoprotein. In survival analysis, moderate and heavy expression of c-erb B-2 were related to poor prognosis (p = 0.032) during a mean follow-up time of 14 years. In conclusion, moderate and heavy expression of c-erb B-2 oncoprotein in TCC seems to be related to more aggressive behaviour whereas low expression of this oncoprotein had no predictive value. No evidence was obtained, however, that the expression of c-erb B-2 concoprotein alone would determine the biological behaviour of TCC.

Aneuploidy↗

Prognostic factors in prostatic adenocarcinoma assessed by means of quantitative histology.

A series of 91 patients with prostatic adenocarcinoma were retrospectively followed up for an average of 15.6 years. The biopsies of the primary tumours were analysed using morphometry for six nuclear features, mitotic-activity index (MAI) and volume-corrected mitotic index. The histological grading of the tumours into three grades was done, and perineural infiltration and lymphatic infiltration were estimated. Clinical stage (p = 0.0137), lymphatic infiltration (p = 0.076) and histological grade (p = 0.1603) were the best predictors of survival in univariate analysis. A multiparameter analysis of progression in T category disclosed the MAI to be the most important single prognostic factor (p = 0.0276). Histological grade predicted progression in M category (p = 0.0166) in the same analysis. In intracapsular T1-T2 tumours, the SD of nuclear perimeter (p = 0.008) was shown by a multivariate analysis to be the most important predictor of progression. Progressed T1-T2 tumours had higher mitotic index values (p = 0.0215). The results advocate the use of mitotic indexes and morphometric measurements instead or as an adjunct of the conventional histological grading while predicting the progression of prostatic adenocarcinoma.

Adenocarcinoma↗

Prognostic factors in human pancreatic cancer, with special reference to quantitative histology.

A retrospective clinicopathologic study was done on 111 patients with a pancreatic ductal adenocarcinoma. The mean follow-up period was 6 years. By means of interactive morphometry six nuclear morphometric features were measured in biopsy specimens from the primary tumours. Volume-corrected mitotic index (M/V index) was estimated in the same sections. Histologic grading was done in accordance with the WHO. The M/V index (p = 0.002), the nuclear area of the 10 largest nuclei (NA10) (p = 0.025), the histologic grade (p = 0.0956), the nuclear area (NA) (p = 0.038), the standard deviation of the nuclear perimeter (SDPE) (p = 0.033), and the standard deviation of the nuclear area (SDNA) (p = 0.0430) predicted survival in univariate analysis. The type of surgery performed was a significant prognosticator too (p = 0.0131). A multifactor regression analysis of survival including clinical and histologic factors identified the M/V index as the most important prognosticator (p = 0.009), followed by the type of surgery performed (p = 0.022). Other histologic factors had no independent prognostic value. Our results suggest the use of morphometric features instead of the conventional histologic grading in predicting survival of pancreatic ductal adenocarcinoma.

Aged↗

Hormone receptors as prognostic factors in female breast cancer.

The oestrogen (ER) and progesterone receptor (PR) status in a series of 281 women with breast cancer (followed up for a mean of 8.5 years) was correlated with eight histological variables, seven nuclear morphometric factors and two mitotic indices. Sex steroid receptor status was not significantly related to tumour size, axillary lymph node status or tumour recurrence. Sex steroid receptors were related to histological grade (P less than 0.0001), nuclear grade (P less than 0.0001), tumour necrosis (P = 0.0003), tumour circumscription (P = 0.0027), inflammatory cell reaction (P = 0.007), intraductal growth pattern (P = 0.0378), and tubule formation (P = 0.0432). Receptor status was also significantly related to nuclear morphometric variables (P less than 0.001) and mitotic indexes (P less than 0.001). In univariate analysis, ER (P = 0.2) and PR (P = 0.1) negatively predicted the recurrence free survival. Cancer related survival was predicted by ER (P = 0.0068) and PR (P = 0.0027). In small (diameter less than or equal to 2 mm) axillary lymph node negative tumours, ER (P = 0.09) and PR (P = 0.1) had some value in predicting the survival. The survival advantage of steroid receptor positive tumours was not due to adjuvant hormone therapy. Sex steroid receptors had independent predictive value in multivariate survival analysis and also in small (diameter less than or equal to 20 mm) tumours. The results indicate that sex steroid receptor negativity is related to several malignant histological features in breast cancer and hormone receptors have prognostic value. Their prognostic influence seems to be mediated through the different proliferation rates in receptor positive and negative breast carcinomas.

Breast Neoplasms↗

Nuclear morphometry and mitotic indexes as prognostic factors in breast cancer.

The primary tumors of 106 female patients with breast cancer (with a mean follow-up of 17 years) were analysed for prognostic factors, with special emphasis on improved prognostic prediction of the small axillary lymph node-negative tumours. In addition to classic prognostic variables (histological type, nuclear grade, tumor size, node involvement), six morphometrically determined nuclear variables (mean nuclear area, SD of nuclear area, mean area of the 10 largest nuclei, maximum nuclear diameter, shortest nuclear diameter, mean nuclear perimeter, and SD of nuclear perimeter) and two mitotic indexes (mitotic activity index (MAI) and volume corrected mitotic index (M/V-index] were measured and related to the patient survival data. Mitotic indexes (p less than 0.001) as well as nuclear morphometric features (p less than 0.001) accurately predicted axillary lymph node involvement at operation. The axillary metastases that developed during the follow-up were also significantly related to mitotic indexes (p less than 0.001). The same indexes also predicted the recurrence free survival (p less than 0.001). The best predictors of cancer related survival were axillary node status and the mitotic indexes at the time of diagnosis (p less than 0.001). The potential of the M/V index in predicting the patient survival was equal to that of the axillary lymph node status. Of the two mitotic indexes, the M/V index was superior to the MAI in survival analysis. The results had us to advocate the inclusion of the newly introduced M/V index in the prognostic factors used in predicting the biological behaviour of breast cancer.

Aged↗

Nuclear morphometry in human pancreatic adenocarcinoma; relation to histological grade, clinical stage, and survival.

A retrospective study was performed on 63 pancreatic cancer patients diagnosed during the years 1970-1988. The mean follow-up time of all individual patients was 6.9 months (range 0-37 months). Histological grade, clinical stage, and 12 morphometric nuclear variables were correlated to the survival of patients. Clinical stage (p = 0.066), histological grade (p = 0.095), and morphometric variables (p = 0.155) predicted survival in survival analysis. Clinical stage (p = 0.029), morphometric variables (p = 0.157), and histological grade (p = 0.306) predicted survival at one year after diagnosis. Morphometric variables divided grade II tumours into two prognostically different groups (p = 0.008) when the mean survival time was used as a classifier. Also the metastasizing potential of pancreatic cancer and lymph node involvement were associated with morphometric variables. Histological grade and morphometric variables were positively correlated (p less than 0.001). On the basis of our results, it seems that nuclear morphometric variables are more efficient or equal to subjective histological grade in predicting survival of pancreatic cancer patients. This result suggests the potential use of nuclear morphometric variables in grading pancreatic adenocarcinomas, and selecting patients for different modes of therapy.

Adult↗