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PubMedDate not supplied

Prognostic value of Ki-67 expression, ploidy and S-phase fraction in patients with pancreatic cancer.

The prognostic value of Ki-67 expression, ploidy and s-phase fraction was evaluated in 133 patients with pancreatic cancer. Formalin-fixed paraffin-embedded surgical specimens of pancreatic ductal adenocarcinomas were stained with a polyclonal Ki-67 antibody. Ploidy and s-phase fraction was assessed by flow cytometry. The median percentage of Ki-67 positive nuclei was 26% (range 0-90%). The level of Ki-67 immunoreactivity was associated with TNM-stage, surgical resectability, tumour grade, ploidy and S-phase fraction. Ninetythree patients, with a nuclear expression of Ki-67 in < 50% of malignant cells, had a median survival of 12.8 months compared with 5.5 months for 25 patients with Ki-67 > or = 50% (p = 0.0008). Ploidy (p < 0.0001) and SPF (p = 0.002) were also significant prognostic factors in a univariate survival analysis. In a multivariate analysis, stage (or alternatively resectability), grade, ploidy and postoperative chemotherapy emerged as independent prognostic factors. When ploidy was excluded from the Cox multivariate model, S-phase fraction also predicted prognosis independently. Ploidy and S-phase fraction are independent prognostic factors in patients with pancreatic cancer. A high level of Ki-67 immunoreactivity is also an indicator of poor prognosis but seems to add little prognostic information to that provided by traditional parameters such as stage, resectability and grade.

Adenocarcinoma↗

PubMedDate not supplied

Fibrinolysis components as prognostic markers in breast cancer and colorectal carcinoma.

The impact of prognostic markers on disease-free and overall survival reflects their relative role in tumour biology. Breast cancer and colon carcinoma can be taken as examples to demonstrate the clinical and biological relevance of 'new markers' of neoplastic disease. In breast cancer, receptor-bound urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 seem to play an important role in the dissolution of the surrounding tissue and the formation of tumour stroma. These processes are prerequisites for invasion and metastasis. The study of 'classical' and 'new' prognostic factors showed that uPA and PAI-1 content of breast cancer tissue are strong and independent prognostic factors. Also in colorectal cancer the prognostic relevance of plasminogen activators and inhibitors was analysed. In particular, low tissue plasminogen activator (tPA) levels, as antigen or as activity, high uPA: tPA antigen ratio in corresponding normal mucosa, high levels of uPA-related antigen and activity and of PAI-2 antigen in neoplastic tissue, and high uPA (neoplastic mucosa): tPA (normal mucosa) ratio, were all parameters associated with a poor overall survival. In conclusion, all these observations show the clinical importance of plasminogen activators and inhibitors at tissue levels with respect to cancer development and survival of patients affected by breast carcinoma or colorectal neoplasia. These new prognostic markers will also permit a better patient selection for a possible adjuvant treatment.

Breast Neoplasms↗

PubMed1996

Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system.

We studied the survival of 195 patients with agnogenic myeloid metaplasia (AMM) diagnosed between 1962 and 1992 in an attempt to stratify patients into risk groups. Median survival was 42 months. Adverse prognostic factors for survival were age > 60 years, hepatomegaly, weight loss, low hemoglobin level (Hb), low or very high leukocyte count (WBC), high percentage of circulating blasts, male sex, and low platelet count. A new scoring system based on two adverse prognostic factors, namely Hb < 10 g/dL and WBC < 4 or > 30 x 10(9)/L, was able to separate patients in three groups with low (0 factor), intermediate (1 factor), and high (2 factors) risks, associated with a median survival of 93, 26, and 13 months, respectively. An abnormal karyotype (32 cases of 94 tested patients) was associated with a short survival, especially in the low-risk group (median survival of 50 v 112 months in patients with normal karyotype). The prognostic factors for acute conversion were WBC > 30 x 10(9)/L and abnormal karyotype. Thus, hemoglobin level and leukocyte count provide a simple prognostic model for survival in AMM, and the adverse prognostic value of abnormal karyotype may be related to a higher rate of acute conversion.

Adult↗

PubMed1996

Multivariate analysis of prognostic factors in patients with endometrial cancer.

OBJECTIVE: The prognostic factors of endometrial cancer are closely correlated. A multivariate analysis was carried to compare the importance of each factor. METHOD: A multivariate analysis was performed of 19 clinicopathologic prognostic factors obtained from 144 endometrial cancer patients who had been surgically treated in our hospital between January 1971 and December 1993. RESULTS: Significant prognostic factors according to the Kaplan-Meier method were depth of invasion, vascular invasion, nuclear grade, cervical involvement, lymph node metastases, intraperitoneal cytology, serous adenocarcinoma, DNA ploidy, type of hysterectomy and surgery only or combined with chemotherapy or radiotherapy. Multivariate analysis showed that vascular invasion and nuclear grade were more significant than structural grade, histologic subtype or DNA ploidy. CONCLUSION: Multivariate analysis is useful for extracting important recurrent factors from mutually related prognostic factors. Vascular invasion and nuclear grade are singled out as the most useful histologic prognostic factors.

DNA, Neoplasm↗

PubMed1996

[Prognostic indicators in patients with liver cirrhosis admitted to an intensive care unit].

OBJECTIVES: Assessment of prognosis in patients with cirrhosis admitted to an Intensive Care Unit remains unsatisfactory. The aims of this retrospective study were to determine the survival rates of patients admitted to an Intensive Care Unit, and to identify and validate prognostic indicators associated with a high mortality rate. METHODS: Two hundred and forty three patients with cirrhosis consecutively admitted to the Intensive Care Unit were studied. The main reasons for admission were upper gastrointestinal bleeding (n = 163), coma (n = 43), sepsis (n = 18), and liver failure (n = 13). Patients were divided into two groups: group 1 (n = 121) to identify prognostic indicators associated with a high mortality rate, and group 2 (n = 122) to validate these indicators. RESULTS: Intensive Care Unit and one year survival rates of patients with cirrhosis admitted for upper gastrointestinal hemorrhage were 76 and 50% respectively. These rates were 40 and 8% respectively for patients admitted for other reasons. In group 1, 4 predictive factors found at admission were identified to have independent significance by stepwise logistic regression: grade III or IV encephalopathy, prothrombin index, serum creatinine, and hypoxemia. On the other hand, the presence of shock on admission was associated with a 100% mortality rate. Two prognostic indicators were defined: shock requiring the administration of vasoactive drugs, and the presence of 3 out of the 4 following predictive factors: grade III or IV encephalopathy, mechanical ventilation, prothrombin index < 30%, and serum creatinine > 130 mumol/L. In group 2, the presence of at least one prognostic indicator at admission or during intensive care was associated with a 96% mortality rate. These indicators were present in 69% of patients who died. In 17 patients who died, but survived more than 24 hours in the Intensive Care Unit, indicators were present an average of 6.0 +/- 5.3 days before death. CONCLUSION: Common prognostic indicators may accurately predict death in patients with cirrhosis admitted to an Intensive Care Unit. These indicators could be helpful in identifying patients who will not benefit from intensive care.

Adult↗

PubMedDate not supplied

Expression of p53 and bcl-2 in primary locally confined renal cell carcinomas: no evidence for prognostic significance.

p53 tumor suppressor gene mutations are present in a wide variety of human cancers, and the bcl-2 gene product is considered to prevent apoptosis. However, the significance of these gene products for the aggressiveness of the tumor and correspondingly for the prognosis of patients with renal cell carcinoma (RCC) is unclear. The expression of p53 and bcl-2 gene products was studied immunohistochemically using formalin-fixed paraffinembedded tumor samples of 31 locally confined RCC of patients treated with radical nephrectomy. The significance of these 2 parameters, in addition to tumor stage and malignancy grade, was tested with regard to survival and time of no recurrence using Kaplan-Meier-plots by the log rank test or Tarone's test and the Cox multiple hazard regression analysis (mean follow-up 5.4 years). Only 5 of the 31 RCCs stained positively for p53 and only 2 showed positive bcl-2 staining of tumor cells. Tumor stage (P < 0.002) and malignancy grade (P < 0.007) were statistically significant prognostic parameters for both survival and disease-free period by univariate analysis. In contrast, the detection of either p53 (P > 0.67) or bcl-2 gene product (P > 0.28) had no prognostic impact. Also in the multivariate statistical analysis, neither of the 2 parameters i.e. p53 and bcl-2 expression significantly improved the prognostic impact of the conventional prognosticators stage and grade, if applied in addition. The expression of p53 and bcl-2 seems unimportant as a prognostic factor in locally confined RCCs.

Adult↗

PubMed1997

Prognostic factors of node-negative gastric carcinoma: univariate and multivariate analyses.

BACKGROUND: The presence or absence of lymph node metastasis closely correlates with survival of patients with gastric carcinoma. Although prognostic significance of the number and level of lymph node metastasis has been clarified, clinicopathologic features and prognostic indicators of node-negative gastric carcinoma have not yet been studied. STUDY DESIGN: The records of 435 patients who underwent curative D2 or D3 gastrectomy for gastric carcinoma between 1977 and 1987 were analyzed retrospectively. Clinicopathologic data of 252 patients having no lymph node metastasis were compared with those of 183 patients with lymph node metastasis. Prognostic factors were investigated by univariate and multivariate analyses. RESULTS: Compared with node-positive cases, node-negative cases were characterized by frequent location in the lower two thirds of the stomach (85 percent), tumor size less than 4 cm (54 percent), grossly superficial type (69 percent), and tumor invasion not beyond the muscularis propria (77 percent). The 10-year-survival rate for patients with node-negative tumors was 93.4 percent. Multivariate analysis demonstrated that depth of wall invasion and age of patient were independent prognostic factors. CONCLUSIONS: Node-negative gastric carcinoma is associated with a favorable outcome because of small progression of the disease. The depth of wall invasion and patient age were the most important prognostic factors.

Female↗

PubMed1997

[Prognostic value of insulin-like growth factor I-IGF-I--and its binding protein IGFBP-3 in alcoholic liver disease].

IGF-I is a single polypeptide chain with important anabolic and endocrine activities. The liver is the major source of IGF-I and its binding protein, IGFBP-3. Circulating concentrations of IGF-I and IGFBP-3 are decreased in patients with chronic liver disease and correlate with the severity. The aim of this study was to assess the additional prognostic value of IGF-I and IGFBP-3 in patients entered in a large multicentre study (EMALD). Three hundred and thirty-seven patients with alcoholic liver disease were studied in a randomised placebo-controlled trial of malotilate with a mean follow-up period of 569 days (range: 7-1544). A multivariate Cox regression analysis of pertinent clinical and biochemical variables revealed a significant independent prognostic value of years of alcohol intake, coagulation factors 2, 7, and 10, alkaline phosphatases, serum creatinine, and immunoglobulin M (IGM). When IGF-I or IGFBP-3 were added into this model, a Cox regression analysis showed that either had a significant independent prognostic value. As IGF-I and IGFBP-3 were closely correlated, they contained almost the same prognostic information. Inclusion of IGF-I gave these results: IGF-I (p < 0.03), alcohol intake (p < 0.02), coagulation factors 2, 7, and 10 (p < 0.01), creatinine (p < 0.001), and IgM (p < 0.01) contained independent prognostic information. Inclusion of IGFBP-3 gave these results: IGFBP-3 (p < 0.02), alcohol intake (p < 0.05), coagulation factor 2, 7, and 10 (p < 0.01), creatinine (p < 0.001), and IgM (p < 0.02) were independent predictors of survival. In conclusion IGF-I or IGFBP-3 provides important additional information on survival in patients with alcoholic liver disease.

Adult↗

PubMed1997

p53 expression compared with other prognostic factors in OMS grade-I stage-Ta transitional cell carcinoma of the bladder.

OBJECTIVE: Recent studies have investigated the possibility that p53 protein and some macroscopic tumoral features, such as diameter and focality of the lesion, play a significant prognostic role in bladder cancer progression. A retrospective study was conducted on papillary grade-I stage-Ta transitional cell carcinoma (TCC) of the bladder. METHODS: p53 expression was evaluated using the immunohistochemical method. A group of 31 patients with papillary grade-I and stage-Ta TCC of the bladder with no recurrence or who recurred with no histological grading and staging variation in a 4-year mean follow-up period was compared with 28 grade-I and stage-Ta papillary TCC patients who underwent recurrences and a worsening in histological grading (grade II or grade III) or staging (T1) within the same period of time. The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein products of the mutated p53 tumor-suppressor gene, when independently evaluated in comparison with other tumoral prognostic factors, are associated with tumor recurrence and progression in patients with Ta papillary grade-I TCC of the bladder. RESULTS: Our data show that when a p53 threshold of > 0% was considered, 53.6% of patients with tumor progression in the follow-up period were p53-positive compared with only 16.1% of the nonprogressing group (chi 2 = 6, p = 0.02). On the contrary, p53 failed to show any value in predicting progression when a 5% threshold was considered (chi 2 = 1.12, p = 0.92). The multifocality of the tumoral lesion and recurrent tumor was highly predictive of tumor progression for both variables (chi 2 = 5.16, p = 0.003, and chi 2 = 0.23, p = 0.006, respectively). Multivariate analysis revealed p53 nuclear overexpression (at a threshold of > 0%) to be a single valuable prognostic factor of progression (OR = 10.20, p = 0.009) and recurrence (OR = 54.19, p = 0.01). CONCLUSIONS: Our results lead to the conclusion that p53 immunohistochemical detection has no prognostic value in predicting tumoral relapse or progression of TaGI TCC of the bladder when a 5% positivity threshold is considered. On the contrary, when a p53 nuclear labelling of > 0% is considered as positive staining, this tumor marker becomes highly predictive of tumor recurrence and progression. These findings seem therefore to suggest the use of a slight p53 positivity (> 0%) as a valid tool in predicting the clinical behavior of TaGI bladder TCC. The prognostic impact of a multifocal lesion and a recurrent tumor as markers of progression is also confirmed by these results.

Aged↗

PubMed1997

p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer.

BACKGROUND: The clinical significance of p53 overexpression in patients with ovarian carcinoma is uncertain. Previous studies have yielded conflicting results and have been hampered by small patient populations, failure to account for other well-known prognostic variables in multivariate analysis, and failure to account for the grade of p53 overexpression. The aim of this study was to investigate the independent prognostic significance of p53 overexpression in patients with primary ovarian epithelial cancer (POEC). METHODS: Tumors obtained from 221 patients with primary ovarian epithelial cancer (POEC) (Stages I-IV) were studied for p53 overexpression semiquantitatively by immunohistochemical techniques. The median duration of follow-up of surviving patients was 7 years. The presence or absence and degree of p53 overexpression were correlated with the clinicopathologic features of the study population and overall survival. Survival curves were constructed according to the Kaplan-Meier method, and differences in survival were assessed with the log rank test. The prognostic significance of p53 overexpression for survival was assessed in a multivariate analysis with the Cox proportional hazards model. RESULTS: One hundred seven tumors (48.4%) exhibited p53 overexpression. The overexpression was graded as mild in 16.7% of cases, moderate in 5.9%, and strong in 25.8%. p53 overexpression was associated with advanced stage (P = 0.04), higher grade (P = 0.0003), serous histology (P = 0.0018), and patient age > 61 years (P = 0.013). In univariate analysis, p53 overexpression was a significant prognostic factor (P = 0.049 for any degree of overexpression, P = 0.03 for strong overexpression). However, in multivariate analysis, after adjustment for stage and size of residual tumor following cytoreductive surgery, p53 overexpression did not retain statistical significance. Survival curves for patients with different stages and grades of tumor differentiation did not demonstrate a difference in survival among patients with no p53 overexpression, compared with those who demonstrated any degree of p53 overexpression or compared with those who demonstrated strong p53 overexpression. CONCLUSIONS: p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer.

Adenocarcinoma↗

PubMed1997

[Clinical course of superficial transitional carcinoma of the bladder without poor prognostic factors].

OBJECTIVES: Surface carcinoma of the bladder shows a high incidence of tumour recurrence that require frequent examinations associated to potential morbidity. This paper analyses our series of patients with vesical tumours with no known unfavourable clinical prognostic factors, aiming to detect low risk groups where it may be feasible to change the usual follow-up criteria. MATERIAL AND METHODS: Between 1983 and 1996, 503 patients with vesical cancer, 388 of which 388 were primarily surface tumours, were monitored. The study analyzed 24 patients with surface transitional carcinoma with no unfavourable prognostic factor, i.e. Ta tumours, grade 1, single, under 1 cm, negative urine cytology and multiple negative vesical biopsies. This group was then compared to a control group comprising all other patients with surface tumours in our series (364 patients), and the prognostic factors were assessed based on the disease-free interval, progression-free interval, and overall and tumour-specific survival. Also the recurrence-free interval from the first endoscopic control at 3 months after transurethral resection, were studied according to Parmar's criteria. RESULTS: With a mean follow-up of 53 months, 37% patients in the study group have relapsed versus 41% in the control group (n = 0.9), after 2 years on average. Actuarial curves in the control group reveal statistical significance for higher degree tumours recurrence. No grade progression has occurred in the study group versus 9% in the control group. No patient evolved to T2 versus 5% in the control group; also in this group, 5% patients died because of their tumour versus none in the study group. The 24 patients in the study belong to group 1 in Parmar's low risk, while the remainder of patients in the control group ranked according to these criteria have demonstrated an unfavourable statistical significance (p < 0.01) in patients with early relapse. CONCLUSIONS: Good results obtained in the evolution of patients with surface tumours with no unfavourable prognostic factors are due to the strict monitoring they undergo in order to detect early relapses. However, 37% of recurrences in this group does not allow to modify the usual follow-up schedule. In our experience, Parmar's criteria does not contribute any benefit over classical criteria to evaluate prognostic factors in surface vesical cancer.

Actuarial Analysis↗

PubMedDate not supplied

Preoperative serum levels of CEA and CA 19-9 and their prognostic significance in colorectal carcinoma.

UNLABELLED: The prognostic information provided by preoperative serum CEA, CA 19-9 antigen assays as compared with the classical prognostic factors (age, sex, tumor infiltration, tumor stage (Dukes') and R-classification) in 495 patients with colorectal carcinoma was analysed. PATIENTS AND METHODS: Survival function estimates were calculated according to Kaplan-Meier. The patients were separated into two groups according to the preoperative marker levels. Fixing specificity at 100% for healthy people, cut off levels were calculated. Survival curve differences were assessed using the log-rank-test. Multivariate Cox's proportional hazard regression analysis was performed. The Mantel-Haenszel method was used to assess the survival rate of patients with colorectal carcinoma and high versus low levels of tumor-associated antigens according to tumor stages. The study was performed on the frozen sera (stored at -80 degrees C) of 495 patients with histologically proven colorectal carcinoma. RESULTS: The Dukes' stages (log-rank chi-square = 231.9; P < 0.0001) represent the best prognostic factor besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA shows a log-rank chi-square of 71.4. Thus, CEA and CA 19-9 can be used to discriminate two groups of patients with significantly different survival times (P < 0.0001). The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis (Cox's model). Estimated relative risks of death adjusted for tumor stage were 5.5 for Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C versus Dukes' stage D, respectively and an increasing relative risk of 27.5 for Dukes' stage A versus Dukes' stage D (P < 0.001). The relative risk for preoperative CA 19-9 serum concentrations (> or = 60 U/mL versus < 60 U/mL) was 2.3 (P < 0.001) for preoperative CEA concentrations (> or = 4 ng/mL versus < 4 ng/mL) 1.4 (P < 0.07). For CEA the 2-years survival rates in the group of patients with preoperative serum concentrations > or = 4 ng/mL versus < 4 ng/mL and Dukes' stage D were 16% versus 38%, in Dukes' stage B/C 73% versus 91% and in Dukes' stage A 100% versus 98%. For CA 19-9 the 2-years survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and Dukes' stage D were 10% versus 39%, in Dukes' stage B/C 58% versus 87%. In the group of patients with Dukes' stage A with serum levels > or = 60 U/mL a 2-year survival rate of 100% was found. In the corresponding group only one patient exists. CONCLUSION: The postoperative Dukes' classification provides the best prognostic information besides the preoperative values of CA 19-9. The predictive information provided by the preoperative CA 19-9 serum level is additional to that obtained from the other factors investigated.

CA-19-9 Antigen↗

PubMed1997

The prognostic value of p53 nuclear overexpression and MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder.

BACKGROUND: There is controversy regarding the value of biologic markers as prognostic indicators independent of clinicopathologic parameters in transitional cell carcinoma (TCC) of the bladder. The authors examined the prognostic value of p53 tumor suppressor gene expression and the proliferative marker MIB-1 in TCC of the bladder. METHODS: Fresh frozen samples from 114 TCCs of the bladder and 13 normal bladders were studied by immunohistochemistry, using monoclonal antibodies MIB-1 for proliferation and PAb 1801 for p53 nuclear overexpression. Scores were determined in each case by counting at least 500 nuclei per slide in 3-5 selected regions. Patients were stratified for both markers into two groups for time-event analysis, according to the median number of nuclei stained. Patients with nuclear staining below the median value of the score were considered negative in the statistical analysis. Quantitative immunostaining was analyzed in relation to the time to recurrence, progression, and cancer death, and compared with clinical and pathologic parameters for prognostic significance in univariate and multivariate analysis (stepwise logistic regression). RESULTS: Median nuclear overexpression of p53 was 22% and that of MIB-1 28%. There was a strong association between proliferation and p53 nuclear overexpression (P < 0.0001). Progression free and disease specific survival rate estimates (log rank test) were significantly lower in patients with p53 or MIB-1 scores above 22% and 28%, respectively. Multivariate analysis indicated that stage as well as p53 and MIB-1 immunostaining provided independent prognostic information. CONCLUSIONS: Quantitative immunohistochemical evaluation of nuclear p53 and MIB-1 immunostaining inexpensively provides prognostic indicators in cases of TCC of the bladder.

Antibodies, Monoclonal↗

PubMed1997

Prognostic factors in gastric cancer.

BACKGROUND: Despite gastric cancer being common, its prognosis has not been improved significantly in recent years. Now, greater insight has been gained into the biological properties of tumour cells, how they become malignant and what mechanisms they may use to invade and metastasize. This involves tumour-associated protease systems, loss or mutation of adhesion molecules and changes in genetics. The view of gastric cancer is changing: it is not only a solid tumour but also exhibits a minimal residual disease component even in the early stages of disease. Such biological tumour characteristics may provide new prognostic factors and also potential new therapeutic options. METHODS: This is an update of prognostic factors in gastric cancer, emphasizing new biological features, some of which have been investigated by this group over the past few years. Current results are discussed in the light of 212 references obtained from the Medline database from 1979 to 1997. RESULTS: There is high probability that some of the factors reviewed, such as c-erbB-2, individual course and phenotyping of disseminated tumour cells will become significant new prognostic variables. This is true also, to a lesser extent, of cathepsin D, matrix metalloproteinase 2 combined with activators or tissue inhibitor of metalloproteinases 2, CD44, E-cadherin, p53 and cripto. Plasminogen activator inhibitor 1 (PAI-1), a member of the urokinase-type plasminogen activator (uPA) system, can already be defined as an established new prognostic factor in gastric cancer. CONCLUSION: PAI-1 should be considered prognostically in addition to established tumour classifications. Moreover, the uPA system is a target for future therapeutic concepts. Further analysis of factors describing tumour biology should lead to new, functionally orientated, tumour classifications in gastric cancer.

Cell Adhesion Molecules↗

PubMedDate not supplied

Simultaneous immunohistochemical and biochemical hormone receptor assessment in breast cancer provides complementary prognostic information.

The prognostic value of the biochemical and the immunohistochemical assessment of estrogen- and progesterone receptor (ER, PR) status was tested in 111 breast cancer patients, mostly focusing on whether the results reveal complementary prognostic information. The biochemical receptor analysis was performed on snap-frozen tumor tissue using a standard protocol (ER-DCC, PR-DCC). The immunohistochemical staining was done on 4 microns thick paraffin sections and was evaluated semiquantitatively (ER-IHC, PR-IHC) and immunohistometrically by means of image analysis (ERMEAN, PRMEAN). 74% of the ER-DCC and 50% of the PR-DCC assays were interpreted as positive. The positivity rates of the immunohistochemical reactions ranged between 78% and 81% for ER and between 66% and 82% for PR, depending on the interpretation mode. The concordance rate for the DCC method was 68%, and ranged between 77% and 85% for the immunohistochemical results on paraffin sections. ER-DCC and PR-DCC showed a better survival for receptor-positive patients; however, this tendency was only statistically significant for the PR-DCC (p = 0.0294). Patients with immunohistochemically determined ER- or PR-positivity revealed a significantly better survival than receptor-negative patients, the effect being stronger for the progesterone receptor (ER: p = 0.0253, PR: p = 0.0005). Combining the different methods and receptors in a multivariate analysis, we observed that a) ER and PR reveal complementary prognostic information to each other after immunohistochemical determination (p < or = 0.0018) and that, b) complementary prognostic information was also obtainable by comparing the biochemical and the immunohistochemical PR-analysis (p < or = 0.0084); slightly more significant results were obtained for ERMEAN and PRMEAN compared to ER-IHC and PR-IHC. Considering the lymph node status and a combined receptor analysis (PR-DCC, ERMEAN, PRMEAN) as the two strongest prognosticators in multivariate Cox models, the combined receptor analysis was able to discover for each of the three groups of NO- and N1-patients different survival probabilities (p < 0.0001). In conclusion, the ER-DCC appears to be dispensable in all patients. In lymph node-negative patients, the PR-DCC has no outstanding merit, indicating that the neccessity of this method is also controversial. In priamry tumors of lymph node-positive patients, however, all three remaining types of receptor analysis should be evaluated for their therapeutic implications.

Breast Neoplasms↗

PubMed1998

Prognostic factors in metastatic germ cell tumors.

Metastatic germ cell cancer is a very heterogeneous group with respect to prognosis under cisplatinum-based chemotherapy. The main determinants of complete response and survival are not only the extension of the metastases but much more the biology of the underlying tumor which is represented by the location of the metastases (pulmonary versus nonpulmonary visceral metastases (liver, bone, central nervous system) and the level of the marker elevation (AFG, HCG, LDH). Using these parameters patients with seminoma can be in two or three prognostic divided groups, depending on the model used; nonseminomatous germ cell cancer can be divided in three prognostic groups (good, intermediate and poor prognosis) with a 5 year survival of 90%, 70%, and 50%, respectively. The rate of marker decline and AFP- "surge" are not proven to be significant indicators of prognosis after the start of chemotherapy. Also, molecular markers i12p, p53, Rb, DNA-repair-capacity, etc, currently do not contribute to the prognostic models. In conclusion, with the present available prognostic models the patients with seminomatous as well as nonseminomatous cancer can be attributed to different prognostic groups for first-line as well as salvage treatment. This allows to the selection of patients for a risk adapted treatment and for the investigation of less toxic regimen for good prognosis patients and more aggressive protocols for intermediate and in particular poor risk patients.

Biomarkers↗

PubMedDate not supplied

Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in a series of 825 cases of breast cancer: major importance of the mitotic count as a component of both grading systems.

The most commonly used system in Europe for breast carcinoma was developed by Scarff, Bloom and Richardson (SBR). It was recently modified by Elston and Ellis and significant improvement in reproducibility has been shown by using precise grading guidelines. This study investigated whether the use of this new grade (defined as the Nottingham grade, NG) would improve the prognostic stratification of patients. The respective prognostic value of the two grading schemes was compared in a retrospective series of 825 patients uniformly treated for a small invasive breast carcinoma and followed for a median of 6 years. Univariate and multivariate analysis showed that both histological grades were strongly correlated to overall and metastasis free survival. We have separately analysed the prognostic value of each of the three components used to assess the two grading systems and found that the mitotic index was the only significant prognostic factor for 5 year survival. Univariate analysis showed the count to be more discriminant in the NG scheme (p = 0.0006) than in the SBR scheme (p = 0.04). However, in univariate and multivariate analysis, the prognostic value of the global NG was not significantly better than SBR grade. This may be related, in part, to an uneven distribution of cases reflected by a much lower number of cases with a high mitotic index in the NG system (2%) than in the SBR system (10%). Our study emphasizes the importance of the mitotic count in assessing the prognosis of breast cancers and indicates that the factors which condition this count (tissue processing, microscopic observation, threshold) must be well standardized and controlled.

Adult↗

PubMed1998

[Primary gastrointestinal lymphomas: response to eradicative therapy and prognostic factors in 52 patients].

BACKGROUND: To analyze the response to eradicative therapy and prognostic factors in 52 patients with primary gastrointestinal lymphoma (PGIL) diagnosed at a single institution in a 13 year period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the Working Formulation. Clinical stage was determined by the Ann Arbor system modified by Mushoff. The results of therapy as well as the influence of such characteristics on complete remission (CR), disease-free survival (DFS) and overall survival (OS) were studied. RESULTS: Mean age of the series was 53 years (SD 15). Thirty patients were males. HIV infection preceded PGIL diagnosis in 10 cases. Seventeen had bad performance status (ECOG 2-4) and 30 B symptoms. The PGIL localization was gastric in 31 cases and 29 had a low grade malignant lymphoma. B phenotype was demonstrated in 98% and 22 patients presented advanced stages (IIE2-IV). Treatment was radical surgery followed by intensive chemotherapy in 32 cases, intensive chemotherapy alone in 17, and surgical resection in 3. CR was obtained in 34 patients and 6 of them relapsed. The projected DFS from CR at 9 years was 72% and OS was 26%. CR and survival were not influenced by PGIL localization and treatment type. The main unfavourable prognostic factors were advanced stage (CR and OS), B symptoms (DFS and OS) and advanced ECOG score (CR, DFS and OS). Previous HIV infection had an independent prognostic influence on both CR and OS. CONCLUSIONS: In patients with PGIL, the achievement of CR, DFS and survival have been independent of the type of eradicative treatment used. Performance status, B symptoms and clinical stage have been the main prognostic factors. HIV infection carried an independent prognostic significance.

Adult↗