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PubMed2026

Construction of molecular signatures based on the co-expression network of NECSO-related gene TRPM4 and its prognostic value in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) demonstrates significant prognostic variability that is not entirely accounted for by traditional staging systems. Necrosis by sodium overload (NECSO) is an emerging programmed cell death pathway, but its clinical relevance in HCC remains undefined. Therefore, this study aimed to identify TRPM4-associated core genes, develop and validate a prognostic signature, and investigate its relationship with the tumor immune microenvironment, tumor mutational burden, and single-cell expression patterns in HCC. METHODS: We integrated transcriptomic, clinical, and mutational datasets from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) (n=421) and Gene Expression Omnibus (GEO) cohorts (n=115) to identify genes co-expressed with TRPM4-a key NECSO mediator-and those differentially expressed in HCC. A prognostic signature was developed using least absolute shrinkage and selection operator (LASSO)-Cox regression and validated through survival analysis, time-dependent receiver operating characteristic (ROC) curves, and multivariate Cox regression analysis. The immune landscape was characterized using CIBERSORT, somatic mutation data were used to calculate tumor mutational burden (TMB) and assess its correlation with the risk score, and single-cell RNA sequencing (scRNA-seq) resolved cell-type-specific expression patterns. RESULTS: From 294 TRPM4-associated core genes, we identified an 11-gene signature (BRSK1, MMP1, GRIN2D, GP6, MYOM2, N4BP3, CCDC112, TSEN54, MAP3K9, SPP1, B3GNT4) that independently predicted overall survival (OS) (hazard ratio =5.419, P<0.001) with areas under the curve (AUCs) of 0.779, 0.693, and 0.701 at 1, 3, and 5 years. These values were superior or comparable to conventional clinicopathologic variables after direct comparison. High-risk patients exhibited an immunosuppressive microenvironment, characterized by enrichment of M0 macrophage, a higher M2/M1 ratio (P<0.001) and distinct immune checkpoint profiles. When integrated with TMB, the prognostic stratification was further refined: high-TMB/high-risk patients had poorest outcomes (median OS, 15.3 months), while low-TMB/low-risk patients had the most favorable survival (median OS, 68.7 months). Single-cell analysis revealed that MMP1 was induced in cancer-associated fibroblasts (CAFs) and SPP1 was downregulated in macrophages, single-cell risk scores confirmed TAFs and macrophages as the main contributors to the prognostic model. CONCLUSIONS: The TRPM4-centered 11-gene signature provides robust and independent prognostic stratification in HCC by integrating immune, mutational, and single-cell features. This signature serves as a potential tool for prognostic evaluation and may help inform immunotherapeutic strategies for HCC.

Hepatocellular carcinoma (HCC)↗

PubMed1992

Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy.

Three hundred forty-five patients with invasive carcinoma of the uterine cervix, Stages Ib (211 patients) and II (134 patients), underwent radical hysterectomy and pelvic lymphadenectomy. The influence of histologic factors including histologic subtype, maximum depth of cervical stromal invasion, degree of stromal invasion, longitudinal tumor diameter, lymph-vascular space invasion, corpus invasion, parametrial invasion, vaginal invasion, and pelvic lymph node (PLN) metastases on survival were examined by multivariate analysis. Univariate analysis revealed that all the variables except corpus invasion and vaginal invasion were significant in survival (P less than 0.05). Among these variables, however, PLN metastases, histologic subtype, and longitudinal tumor diameter were identified as independent and significant prognostic factors by multivariate analysis using Cox regression models. The prognostic index (PI), defined by the model (an indicator of the patient's place in the prognostic spectrum), was able to divide the patients into three prognostic groups. The key factors in the definition of these groups were (1) squamous cell carcinoma, small tumor diameter, and no PLN metastases for the good prognostic group and (2) PLN metastasis in two or more node groups, adenocarcinoma with one positive PLN group, or squamous cell carcinoma with one PLN group and large diameter for the poor prognostic group. These prognostic findings could predict the prognosis more precisely than that of clinical staging.

Adult↗

PubMed1992

Mammographic growth rate, DNA ploidy, and S-phase fraction analysis in breast carcinoma. A prognostic evaluation in a screened population.

BACKGROUND: The authors examined prognostic factors in 158 cases of breast carcinoma with known mammographic tumor volume doubling times (DT). METHODS: The tumors were retrospectively reexamined histologically and flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) was performed on archival paraffin-embedded material in each case. Life tables and Cox multivariate analyses were used for statistical evaluation of prognostic factors. RESULTS: In univariate analysis of survival data, clinical and pathologic stage, histologic grade, the presence of axillary lymph node metastases, and SPF were significant prognostic predictors, but mammographic DT and DNA ploidy were not. SPF also contributed prognostic information in the subgroup of carcinoma cases detected by screening. In a Cox multivariate analysis, SPF, the presence of axillary lymph node metastases, and Stage II-III disease (as opposed to Stage I disease) were independent significant predictors of survival. In univariate analyses of distant disease-free survival, clinical and pathologic stage, tumor size, histologic grade, the presence of involved axillary nodes, DT, and SPF all were significant prognostic factors. CONCLUSIONS: SPF, stage, and lymph node status were important prognostic factors in this patient material with predominantly small and node-negative breast carcinomas, whereas DNA ploidy and mammographic DT provided less prognostic information. The prognosis of carcinoma detected during screening did not differ significantly from that of breast carcinoma discovered otherwise in this selected patient group.

Adult↗

PubMed1994

Prognostic factors in pulmonary fibrohistiocytic lesions.

BACKGROUND: The spectrum of pulmonary fibrohistiocytic lesions (PFL) ranges from benign fibrohistiocytoma or inflammatory pseudotumor, fibrohistiocytic type (IP), to fibrohistiocytic lesions of borderline malignant appearance (B), to unequivocal malignant fibrous histiocytoma (MFH). The authors reviewed a spectrum of PFL in an attempt to define their natural history and establish independent factors of prognostic significance. METHODS: Thirty-one fibrohistiocytic lesions were analyzed by multiple clinical, gross, and microscopic factors. Prognostic factors were evaluated by univariate and multivariate Cox proportional hazards models. RESULTS: After histopathologic review, the cases were classified into IP (15 cases), B (3 cases), and MFH (13 cases). IP tended to occur in younger patients (median age, 30 years; range, 11-64 years) than did MFH (median age, 54 years; range, 12-81 years) (P = 0.03). All 15 patients with IP and 3 patients with B survived. Local recurrence developed in 2 patients with IP and 6 patients with MFH. Distant metastases occurred in 7 patients with MFH. Eight of 13 patients with MFH died of disease, with a median survival time of 16 months (range, 6-36). For all pulmonary fibrohistiocytic lesions, univariate Cox regression analysis disclosed several statistically significant prognostic factors associated with mortality: metastasis (P = 0.0005), significant necrosis (P = 0.0015), local recurrence (P = 0.003), bizarre giant cells (P = 0.0282), mitoses greater than or equal to 3 per 50 high-power fields (P = 0.0286), stage at surgery (P = 0.002), high cellularity (P = 0.0267), and poor circumscription (P = 0.0294). Other parameters (age, sex, symptoms, laterality, location, atypical mitoses, nuclear pleomorphism, degree of fibrosis, and size) were not significant prognostic factors. By multivariate Cox regression analysis, metastasis was the most significant individual parameter (P = 0.002), overriding all other prognostic factors. With metastasis removed from the model, local recurrence (P = 0.0199) and necrosis (P = 0.037) were the other significant independent prognostic factors. CONCLUSIONS: Certain individual clinical, gross, and microscopic features have prognostic relevance in determining survival time in pulmonary fibrohistiocytic lesions.

Adolescent↗

PubMed1994

Prognostic factors and significance of chemotherapy in patients with recurrent or metastatic transitional cell cancer of the urinary tract.

BACKGROUND: Prognostic factors for patients with disseminated transitional cell carcinoma of the urothelium (TCC) has been examined only in patients selected for studies with chemotherapy. This study was performed to determine important prognostic factors in patients with disseminated TCC and evaluate the impact of chemotherapy. METHODS: The prognostic factors for survival were analyzed in 240 patients with disseminated TCC admitted from 1976 to 1992. Information on prior medical history, baseline variables, and treatment were related to survival after dissemination. Both univariate and multivariate analyses were performed to identify factors of independent importance. RESULTS: Univariate analyses indicated that performance status; hemoglobin; leukocyte count; platelet count; concentrations of serum creatinine, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase; hydronephrosis; bone metastases; disease extension; and chemotherapy were related significantly to survival. Multivariate analysis demonstrated that a good performance status, a normal alkaline phosphatase concentration, and a normal serum creatinine concentration were independent prognosticators for long survival. When chemotherapy was included in the analysis, it was found to be the most important independent prognostic factor in conjunction with alkaline phosphatase and performance status. CONCLUSION: This study has established the importance of performance status and alkaline phosphatase as the most important prognostic factors of survival in patients with disseminated TCC regardless of treatment. Chemotherapy was found to be an independent prognostic variable that indicates a possible prolongation of survival in patients receiving chemotherapy.

Adult↗

PubMed1990

Prognostic factors for patients with diffuse large cell or immunoblastic non-Hodgkin's lymphomas: experience of the non-Hodgkin's Lymphoma Pathologic Classification Project.

Prognostic factors for long-term survival of 312 patients with diffuse large cell or immunoblastic non-Hodgkin's lymphoma are presented based on analysis of the multiinstitution clinicopathologic study sponsored by the National Cancer Institute. At the time of analysis, 75% of the patients had died and the median follow-up for patients still alive was 11 years. The distribution of Ann Arbor stages was 21% stage I, 32% stage II, 17% stage III, and 30% stage IV. Factors of prognostic significance for survival included age, stage, histologic subtype, presence of B symptoms, size of the largest lesion, number of extra-lymphoid organs involved, and extent of lymphatic involvement. Recursive partitioning analysis suggested a prognostic classification system based on stage, age, size of the largest lesion, and presence of mediastinal involvement. Stage I patient less than 50 years of age had a 10 year survival rate of 65% compared to 36% for older stage I patients. Stage II patients less than 65 years old without bulky lesions or mediastinal involvement had a 10 year survival rate of 45% compared to 10% for the poorer risk stage II patients. Although statistically significant prognostic factors were identified for the stage III/IV patients, they were not strong discriminants of 5-10 year survival rate. Because of the correlation among potential prognostic factors, there is no uniquely best classification system. Reasons for discrepancies among reported prognostic factor analyses are discussed, and a prognostic grouping that synthesizes our results with those of others is proposed.

Adult↗

PubMedDate not supplied

FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973-87 SEER cases of cancers of the endometrium, cervix, ovary, vulva, and vagina.

The prognostic impact of FIGO stage, histology, histologic grade, age and race in survival for cancers of the female gynecological (cervix, endometrium, ovary, vulva, vagina) were examined using cases obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program that were diagnosed between 1973 and 1987. Utilizing Cox proportional hazards modeling and relative survival rates analysis of 17,119 cases of cervical cancer indicated that the International Federation of Gynecology and Obstetrics (FIGO) stage, histology, histological grade, lymph node status, and age at diagnosis were all independently prognostic. No evidence was found of survival differences between squamous cell carcinoma and adenocarcinoma. Younger women were not found to have a poorer prognosis, survival declined with increased age. Analysis of 41,120 cases of endometrial cancer indicated that FIGO stage, histology, histologic grade, lymph node status, age at diagnostic, and race were all prognostic factors. Clear cell adenocarcinoma, leiomyosarcoma, and mixed mullerian tumors were all found to have poorer prognosis. Analysis of 21,240 cases of ovarian cancer indicated that FIGO stage, histology, histologic grade, lymph node status, age at diagnosis, presence of ascites, and race were all prognostically significant. Analysis of 2,575 cases of vulvar cancer indicated that FIGO stage, histology, histologic grade, age, and race were all prognostically significant. Analysis of 916 cases of vaginal cancer indicated that FIGO stage, histologic grade, lymph node status, and age are all prognostically significant. Additional analysis of the data by combinations of independent prognostic factors indicates that the interaction of factors may be more predictive of outcome than any one factor separately.

Adenocarcinoma↗

PubMed1995

Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma--results of a multiparametric study.

In the present study we update previous results on the prognostic value of intratumoral microvessel density (IMD), determined immunocytochemically using the monoclonal antibody CD-31 and a standard streptavidin-immunoperoxidase technique, published in the J Clin Oncol 12:454-466, 1994. This study was undertaken in those 211 node-negative breast cancer (NNBC) cases of that series of which we had pathological material available to determine all the prognostic indicators. The median period of follow-up has been extended to 78 and 80 months for relapse-free survival (RFS) and overall survival (OS), respectively, and new biological indicators (i.e. Ki-67 labeling and 67 kDa laminin receptor expression) were included in the analysis. The main results obtained are: i) a confirmation that IMD is not associated with the other biological markers studied, i.e. expression of p53 protein, c-erbB-2 protein, 67 kDa laminin receptor, and cell kinetics; IMD was weakly associated only with histological grade (p = 0.053); ii) IMD remains a highly significant prognostic factor for RFS and OS (p < 0.0001 and p = 0.018, respectively) in univariate analysis; iii) in multivariate analysis on RFS, IMD (likelihood ratio test (LRT) = 30.16; p < 0.0001), 67 kDa laminin receptor (LRT = 9.80; p = 0.0017), the IMD/67 kDa laminin receptor interaction (LRT = 8.62; p = 0.0033), tumor size (LRT = 8.56; p = 0.0034), and p53 protein (LRT = 4.96; p = 0.025) are significant and independent prognostic indicators. For OS, only tumor size (LRT = 8.34; p = 0.0038), menopausal status (LRT = 5.16; p = 0.023), p53 protein (LRT = 4.37; p = 0.036), and IMD (LRT = 4.05; p = 0.044) retain a significant and independent prognostic value. The results of this study confirm the prognostic importance on RFS of the variables previously tested, but not of peritumoral lymphatic vessel invasion. A novel finding is that 67 kDa laminin receptor and the IMD/67 kDa laminin receptor interaction are also significant and independent variables. For OS, the results confirm that both IMD and tumor size are significant and independent variables. With prolonged follow-up the novel finding that emerges is the prognostic importance of menopausal status and p53 protein. This new information could be useful for a more accurate selection of high-risk NNBC patients who require careful follow-up and may benefit from adjuvant therapy.

Analysis of Variance↗

PubMedDate not supplied

A method of clinical prognostic staging for patients with rectal cancer.

Methods of prognostic stratification for patients with rectal cancer currently rely solely on the extent of tumor penetration in the surgically excised rectum. Thus stratification according to prognostic factors can be performed only after treatment had been carried out and can play no role in pretherapeutic treatment decisions or in the design of trials of preoperative adjuvant treatment. To devise a method of clinical prognostic staging that could be applied to all patients with rectal cancer, regardless of therapy, the medical records were examined of an inception cohort of 282 patients treated by surgical and nonsurgical methods at three Toronto hospitals during the years 1968 to 1974. Six groups of clinical variables were identified that independently influenced prognosis: the presence or absence of metastatic disease, whether the rectal tumor was fixed or mobile, an annular rectal tumor, and the systemic symptoms of weight loss, anorexia, or weakness, and anemia. A composite method was developed for clinical prognostic staging from these variables and it was found that it created substantial gradients in survival. In patients treated by surgery, for whom comparisons of clinical staging with conventional anatomic staging were possible, clinical staging was as effective a method of prognostic staging as was anatomic staging. Furthermore, the prognostic impact of clinical staging persisted after adjustment for the effects of anatomic staging. This method of clinical prognostic staging should prove useful in making therapeutic decisions and in the design and analysis of clinical trials of alternative treatment for patients with rectal cancer.

Anemia↗

PubMed1992

Prognostic usefulness of hepatic vein catheterization in patients with cirrhosis and esophageal varices.

Clinical and anamnestic data, Pugh score, and size of esophageal varices were obtained in 129 cirrhotics. Hepatic vein catheterization was performed to measure hepatic venous pressure gradient (HVPG), indocyanine green (ICG) intrinsic hepatic clearance, and hepatic plasma flow. During a follow-up period of up to 60 months, 44 patients experienced gastrointestinal bleeding and 54 died. Applying Cox regression analysis, ICG intrinsic hepatic clearance, Pugh score, previous variceal bleeding, and HVPG were the only significant prognostic determinants of survival. In addition, Cox's regression analysis showed that HVPG, Pugh score, size of varices, and previous variceal bleeding all contained significant prognostic information regarding risk of gastrointestinal bleeding. The models were validated using a split-sample technique, and prognostic indexes for death and gastrointestinal bleeding were calculated. The prognostic index predicting death had significantly improved prognostic accuracy over a prognostic index calculated excluding the data obtained from hepatic vein catheterization (P less than 0.05). In conclusion, prognostic accuracy in cirrhosis with portal hypertension is significantly improved by information obtained from hepatic vein catheterization.

Adolescent↗

PubMed1995

Comparison of the prognostic value of four methods to assess mitotic activity in 186 invasive breast cancer patients: classical and random mitotic activity assessments with correction for volume percentage of epithelium.

Proliferation markers and especially the Mitotic Activity Index (MAI) are strong and reproducible prognosticators in invasive breast cancer. Traditionally, the MAI has been defined as the total number of mitoses counted in 10 consecutive high-power fields (objective, x40; numeric aperture, .75; field diameter, 450 microns), in the most cellular area at the periphery of the tumor, with the subjectively highest mitotic activity. No correction for epithelial percentage or cellularity was applied. This study investigates whether the prognostic value of mitotic activity could be improved by a random sampling procedure or correction for percentage of epithelium present. For this purpose the prognostic value of four methods used to assess mitotic activity in invasive breast cancer was compared in 4-microns-thick hematoxylin-eosin (H&E)-stained sections of 186 primary invasive breast cancer patients. These were the MAI, the random MAI (rMAI), the Mitosis per Volume (M/V) Index, and the random M/V Index (rM/V Index). The rMAI was defined as the total number of mitotic figures counted in 10 random fields through the whole outlined tumor at x400 magnification. A correction for the volume percentage of epithelium assessed with stereology yielded the M/V Index and the rM/V Index, respectively. The results of all four methods showed moderate to high correlations. Univariate survival analysis (Kaplan-Meier curves; Mantel-Cox test) confirmed that all four methods had a strong prognostic value (P < .001). The MAI, however, produced the best results (Mantel-Cox value, 17.1). Multivariate analysis showed that all four methods had additional prognostic value to tumor size and lymph node status. The M/V Index provided most additional prognostic information, followed by the MAI. Assessment of rMAI took 20 to 30 minutes on average, about two times longer than MAI. The correction for volume percentage of epithelium took about 10 minutes longer for both methods than the uncorrected methods. In conclusion, the rMAI gives an impression of the mitotic activity through the whole tumor, with almost similar prognostic value as the traditional MAI, especially when correcting for percentage of epithelium. Nevertheless, the MAI is still to be preferred, because the assessment is easy to apply and less time consuming.

Adenocarcinoma↗

PubMed1988

Prognostic value of the simplified Selvester QRS score in patients with coronary artery disease.

The relation of the simplified Selvester QRS scoring system for the estimation of myocardial infarct size to survival was studied in 1,915 nonsurgically treated patients with documented coronary artery disease. Electrocardiograms (ECGs) were scored according to a simplified 29 point QRS scoring system. Using Cox model analyses, QRS scores were found to provide strong prognostic information by themselves (p less than 0.0001). Higher QRS scores were associated with lower survival rates. Patients with a score of 0 had a 1 year survival rate of 95% and a 5 year survival rate of 88%; patients with a score of 10 or more had survival rates of 81 and 52%, respectively, at the same intervals. Directly compared with the presence or absence of Q waves on the ECG, QRS scores provided greater prognostic information (p less than 0.001). When compared with 13 individual factors previously shown to provide the greatest independent prognostic information, the QRS score was the third most powerful individual prognostic factor. It did not contribute independent prognostic information in combination with the whole group, but did provide independent information in combination with the six most predictive factors. Its prognostic information overlapped mostly with clinical factors related to heart failure, and combined best with clinical factors related to the severity of ongoing myocardial ischemia. Because it is inexpensive and simple and maximizes the prognostic information from the ECG, the simplified Selvester QRS scoring system can be a useful clinical descriptor for practitioners and clinical investigators.

Cardiac Catheterization↗

PubMed1991

Analysis of prognostic factors in 766 patients with small cell lung cancer (SCLC): the role of sex as a predictor for survival.

The data of 766 patients participating in three German multicentre trials were analysed with regard to the relationship between baseline characteristics and prognosis in small cell lung cancer (SCLC). The central aim of this analysis has been to evaluate the role of gender as an independent prognostic factor in SCLC. The minimum follow-up period for the 652 male and 114 female patients was 36 months. Female patients were shown to have a higher complete remission rate (35% vs 25%), a superior median survival (ms) (12.1 months (mo) vs 9.8 mo), and a favourable 2-year survival rate (2ys) (19% vs 8%) to male ones. Various other prognostic factors have been proved to be significant, such as extent of disease, clinical performance status, and history of smoking, whereas weight loss prior to chemotherapy and age have been less important factors. We have been able to ascertain that women's responses were better than those of male patients independent of any other relevant prognostic variable. Furthermore, results were found to be even more advantageous for female patients with additional favourable prognostic parameters, i.e. for patients with limited disease (ms 15.2 mo vs 12.0 mo; 2ys 29% vs 9%) or with good performance status (ms 13.4 mo vs 10.4 mo; 2ys 24% vs 7%). A most remarkable observation was made in that the favourable prognostic effect of the female gender was restricted to patients aged less than 60 years (ms 13.3 mo vs 10.1 mo; 2ys 26% vs 5%), whereas for older women no advantages over men's results were established (ms 9.3 ml vs 9.1 mo; 2ys 8% vs 7%). A proportion of 32% of female patients with limited disease aged less than 60 years achieved a 3-year survival rate. We conclude (a) that sex constitutes a major prognostic factor in SCLC and is especially useful as a predictor for long-term survival, and (b) that the favourable prognostic value of the female sex is restricted to younger patients.

Age Factors↗

PubMed1989

[Proliferation index, axillary lymph node status, hormone receptors and age as prognostic factors in primary breast cancer].

A total of 233 primary carcinomas of the breast (n = 68 nodal negative and n = 165 nodal positive) of 77 woman patients of less than 50 years of age and pf 156 women patients of 50 years of age or older were examined for the prognostic significance of a proliferation index (in vitro chemoresistance assay). The prognostic significance of the proliferation index (high vs low proliferation) is compared with other prognostic factors that have already been in clinical use (age, axillary lymph node status, oestrogen and progesterone receptor status). The total median observation period was 4.8 years (3-9.1 years). Determination of the proliferation index proved to be the most important prognostic factor both for premenopausal and postmenopausal, nodal negative and nodal positive primary tumours when assessing the total survival time and the time that remains free from recurrences. A simultaneous assessment of low proliferation index and positive hormone receptor as a so-called low-risk situation shows in comparison to a high-risk situation (high proliferation index, negative receptor status) the most pronounced differences. For premenopausal women (younger than 50 years of age) the hormone receptor status has no prognostic significance as far as our group of patients is concerned, whereas for women of 50 years of age or older the receptor status is of great prognostic relevance. Besides the lymph node status, the proliferation index shows in a Cox regression model the greatest prognostic importance for the further course of a primary carcinoma of the breast.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1991

Prognosis and breast cancer. Recognition of lethal and favorable prognostic types.

Assignment of breast cancer patients to specific prognostic groups has been a relatively empty exercise until the recent acceptance of the effectiveness of systemic chemotherapy. The previous question of who should be so treated has changed in North America to a question of who should not be so treated. The availability of intensive chemotherapy for the worst prognostic groups as well as efficacious, low-toxicity adjuvant chemotherapy has made prognostication mandatory. The current major question is which women with breast cancer will not benefit from chemotherapy. We are actually much better at prognostication than many studies and the current broad search for new prognostic markers would indicate. The assignment of excellent prognosis categories by defined special histologic types or grade of breast cancer as well as other measures recognize women with survival approaching or equaling the general population. Likewise, extremely poor prognosis may be recognized in 20% to 40% of women with breast cancer by the presence of extensive mitoses or high proliferation index (by any modality) and poor differentiation (highest grade). Combined tumor size and nodal status data with high-grade indicates that women with these indicators will die within 2 to 3 years with as high as 80% certainty. The surgical pathologist still determines if cancer is present and must also determine if the tumor is in situ or invasive, its type or grade if invasive, and the extent of in situ component. Considering the diminution in overall size of cancers detected by modern techniques, it is clear that validation of newer prognostic variables will be more useful and will allow more separate determinations if adapted to tissue sections rather than tissue homogenates. The many measures of these carcinomas, such as size and nodal status, make multiparametric assessment of putative prognostic markers mandatory.

Biomarkers, Tumor↗

PubMed1994

Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma.

OBJECTIVE: The authors sought to identify prognostic factors in the management of extremity soft tissue sarcoma. SUMMARY BACKGROUND DATA: The surgical management of soft tissue sarcoma has evolved because of advances in therapy, resulting in increased limb preservation and quality of life. However, identifying a subset of patients most likely to benefit from adjuvant chemotherapy has been difficult to achieve. METHODS: A retrospective analysis of a prospective data base of 182 patients with extremity sarcomas from 1970 to 1992 was performed. RESULTS: A histologic diagnosis of Ewing's sarcoma, synovial sarcoma, and angiosarcoma was associated with a 13-fold increased risk of death compared with liposarcoma, fibrosarcoma, and malignant peripheral nerve sheath histologic types after having adjusted for the other prognostic factors (p < 0.001). In addition to histologic type, high-grade sarcomas (p = 0.018), sarcomas greater than 10 cm in size (p = 0.006), and age at diagnosis (p = 0.016) were found to be important prognostic factors for survival but not for local recurrence. For the first time to their knowledge, the authors showed that mean mitotic activity has prognostic value after having adjusted for other prognostic factors, such as grade (p = 0.005). The only prognostic factors predictive for local recurrence were whether the patient presented with locally recurrent disease (p = 0.0001) or had microscopically positive margins (p = 0.052). CONCLUSIONS: The use of mitotic activity along with grade, size, histologic type, and age at diagnosis is prognostic for survival in extremity soft tissue sarcoma. The use of an objective pathologic feature, such as mean mitotic activity, is also useful in selecting patients for future systemic neoadjuvant or adjuvant trials and primary therapy.

Adolescent↗

PubMed1995

Prognostic factors predictive of survival for truncal and retroperitoneal soft-tissue sarcoma.

OBJECTIVE: The authors identified prognostic factors relevant to clinical outcomes (especially survival) in truncal and retroperitoneal soft-tissue sarcoma. SUMMARY BACKGROUND DATA: These results can be used to optimize surgical management and select patients most likely to benefit from novel therapeutic strategies in future trials. METHODS: A retrospective analysis was performed of a prospectively compiled database of 183 consecutive patients with truncal and retroperitoneal sarcomas seen at the Brigham and Women's Hospital and the Dana Farber Cancer Institute between 1970 to 1994. RESULTS: For truncal sarcoma, multivariate analysis showed that high-grade histology was associated with an eightfold increased risk of death compared with low-grade histology (p = 0.001). In addition to grade, gross positive margin of resection (p = 0.001), microscopic positive margin (p = 0.023), and tumors greater than 5 cm in size (p = 0.018) were important independent prognostic factors for survival. In this series, postoperative radiation therapy for truncal sarcoma was associated with a 2.4-fold decreased risk of death compared with truncal sarcoma patients receiving no adjuvant radiation therapy, having adjusted for the other prognostic factors (p = 0.030). In contrast, for retroperitoneal sarcoma, multivariate analysis showed that high-grade and intermediate-grade histology were associated with a five- to sixfold increased risk of death compared with low-grade histology (p = 0.009). In addition to grade, gross positive margin of resection (p = 0.001) and microscopic positive margin (p = 0.004) were important independent prognostic factors for survival in retroperitoneal sarcoma. Patients who received either preoperative or postoperative chemotherapy for retroperitoneal sarcoma had a 4.6-fold (p = 0.002) and 3-fold (p = 0.010) increased risk of death, respectively, compared with patients receiving no adjuvant chemotherapy, having adjusted for the other prognostic factors. CONCLUSIONS: The histologic grade and the margin of resection are prognostic for survival in both truncal and retroperitoneal soft-tissue sarcoma. Tumor size was an independent prognostic factor for truncal sarcoma, but not for retroperitoneal sarcoma. Postoperative adjuvant radiation was beneficial to overall survival for truncal sarcoma. In this series of patients receiving a heterogeneous mixture of chemotherapeutic regimens-either as preoperative "neoadjuvant" therapy or as postoperative "adjuvant" therapy, there were no beneficial effects on survival compared with nonrandomized patients not receiving chemotherapy.

Adult↗

PubMed1993

Serum thymidine kinase as a prognostic indicator for patients with multiple myeloma: results from the MRC (UK) V trial.

The significance of serum thymidine kinase (STK) as a prognostic indicator for patients with myeloma has been evaluated by determining the pre-treatment level of STK in a retrospective study of 547 patients from the Medical Research Council (MRC) V Myeloma Trial. Overall, STK was a highly significant prognostic factor (Chi 2 = 7.91; P = 0.005). At the time of censor, 23.4% of patients with a presentation STK of < 6 U/l but only 7.9% of the patients with an STK of > 11 U/l were still alive. STK proved to be a highly significant prognostic indicator for the 270 melphalan-treated patients (Chi 2 = 12.37; P = 0.0004) but had no prognostic significance for the 277 ABCM (adriamycin, BCNU, cyclophosphamide and melphalan) treated patients (Chi 2 = 0.29; P = 0.59). When the STK data was stratified for serum B-2-microglobulin (SB2M) it was demonstrated that STK was independent of SB2M and provided additional prognostic information for patients who were treated with melphalan. Thus patients with both a low STK and SB2M had the best prognosis (median survival 1677 d) and those patients with a high STK and SB2M had the worst prognosis (median survival 519 d). STK is a good prognostic marker for patients treated with melphalan but the prognostic significance of STK may disappear with the introduction of new chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗