Prognostic value of the histologic classification of peripheral T-cell lymphoma: a clinico-pathologic study of 71 HTLV-1 negative cases.

The histologic and clinical features of 71 cases of peripheral T-cell lymphoma (PTCL) have been studied. All patients were HTLV-1 negative. The T-cell phenotype was demonstrated by immunohistochemistry on cryostat sections (41 cases) and paraffin-embedded sections (30 cases). All cases were histologically classified according to the updated Kiel classification of non-Hodgkin's lymphoma (low and high-grade) and according to a Working Formulation (WF)-based classification (predominantly small cells, mixed small and large cells, and predominantly large cells). Most cases were in the high-grade group according to both classifications. The prognostic value of these two classifications was comparatively assessed. The analysis of the actuarial survival curves showed that, by using the updated Kiel classification, low-grade PTCL had a survival probability higher than high-grade PTCL although the difference was not statistically significant. Similar results were obtained when the WF-based classification was applied: furthermore, actuarial survival curves of mixed small and large cell PTCL, and of large cell PTCL were rather similar, thus indicating that differentiating these two categories has a limited prognostic value.     

Prognostic Value of the Histologic Classification of Peripheral T-cell Lymphoma: A Clinico-Pathologic Study of 71 HTLV-1 Negative Cases

The histologic and clinical features of 71 cases of peripheral T-cell lymphoma (PTCL) have been studied. All patients were HTLV-1 negative. The T-cell phenotype was demonstrated by immunohistochemistry on cryostat sections (41 cases) and paraffin-embedded sections (30 cases). All cases were histologically classified according to the updated Kiel classification of non-Hodgkin's lymphoma (low and high-grade) and according to a Working Formulation (WF)-based classification (predominantly small cells, mixed small and large cells, and predominantly large cells). Most cases were in the high-grade group according to both classifications. The prognostic value of these two classifications was comparatively assessed. The analysis of the actuarial survival curves showed that, by using the updated Kiel classification, low-grade PTCL had a survival probability higher than high-grade PTCL although the difference was not statistically significant. Similar results were obtained when the WF-based classification was applied: furthermore, actuarial survival curves of mixed small and large cell PTCL, and of large cell PTCL were rather similar, thus indicating that differentiating these two categories has a limited prognostic value.     

Prognostic impact of DNA ploidy pattern,S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) in patients with primary gastric lymphoma

BACKGROUND: DNA ploidy, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) are considered to be significant prognostic factors in non-Hodgkin lymphomas. However, reports on their prognostic importance in gastric lymphoma patients are relatively lacking. METHODS: In the present study, we retrospectively studied the above-mentioned parameters in 29 patients with primary gastric lymphoma; 11/29 had B-low grade mucosa associated lymphoid tissue lymphoma (B-MALT), while 18/29 had diffuse large B-cell lymphoma (DLBCL), according to WHO classification. Proliferative activity was studied by staining against PCNA; in addition, the prognostic significance of DNA ploidy and SPF, as determined by flow cytometry, were investigated and compared to the results of the PCNA stainings. RESULTS: Seven out of 29 patients were found to have aneuploid tumors; DNA index values were >1 for all aneuploid lymphomas. There was no difference in DNA aneuploidy in MALT vs. DLBCL. The mean percentage of SPF was 11.4. SPF was found significantly lower in MALT vs. DLBCL (P < 0.05). The mean percentage of PCNA positive tumor cells was 52.6. PCNA protein expression was significantly lower in MALT vs. DLBCL (P < 0.0001). There was a significant positive correlation between PCNA score and SPF (P < 0.01, by Spearman analysis). DNA ploidy had no impact on survival in the present study. Both SPF and PCNA expression were important prognostic factors in the univariate analysis; however, in the multivariate analysis, the only independent prognostic factor for survival was PCNA expression. CONCLUSIONS: These findings indicate that SPF and PCNA are significant prognostic factors in patients with primary gastric lymphomas. However, in the present study, DNA ploidy had no impact on survival in patients with primary gastric lymphomas.     

Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin's lymphomas

Node biopsies of 30 benign lymphadenopathies and 71 B-cell non-Hodgkin's lymphomas (B-NHLs) were investigated for microvessel and macrophage counts using immunohistochemistry and morphometric analysis. Both counts were significantly higher in B-NHL. Moreover, when these were grouped into low-grade and high-grade lymphomas, according to the Kiel classification and Working Formulation (WF), statistically significant higher counts were found in the high-grade tumours. Immunohistochemistry and electron microscopy revealed a close spatial association between microvessels and macrophages. Overall, the results suggest that, in analogy to what has already been shown in solid tumours, angiogenesis occurring in B-NHLs increases with tumour progression, and that macrophages promote the induction of angiogenesis via the release of their angiogenic factors.     

Histologic subtypes and survival of Chinese patients with non-Hodgkin's lymphomas

The histologic subtypes and survival of 840 Chinese patients with non-Hodgkin's lymphoma (NHL) were reviewed. All cases were classified according to the Rappaport and Kiel systems and the Working Formulation (WF). A low incidence of nodular/follicular lymphomas (12%) was observed. The most common histologic subtypes were diffuse histiocytic, diffuse centroblastic, and diffuse large cell lymphomas, according to Rappaport, Kiel, and the WF, respectively. A high proportion (24%) of the cases were unclassifiable, according to Kiel, because of the precise terms of the classification. The "favorable"-prognosis NHL, according to Rappaport, or the low-grade NHL, according to Kiel and the WF, had a more indolent clinical course. However, except for the nodular mixed (Rappaport) or follicular mixed (WF) lymphomas which appeared to behave like the more aggressive NHL, a plateau was not seen in the survival curves of our patients with other kinds of favorable-prognosis or low-grade NHL, indicating the lack of curative potential of these tumors. The lymphoplasmacytoid lymphoma, according to Kiel, also appeared to have a more aggressive clinical course. A plateau was seen in most of the other survival curves of patients with the more aggressive tumors, indicating the prospect of cure. However, the prognosis of the very aggressive tumors such as the diffuse lymphoblastic and diffuse small noncleaved cell lymphomas, according to the WF, remains very poor with a median survival of less than 10 months.     

Prognostic significance of DNA cytometry in cutaneous malignant lymphomas

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML.     

A new working formulation of non-Hodgkin's lymphomas. A retrospective study of the new NCI classification proposal in comparison to the Rappaport and Kiel classifications

Two hundred thirty cases of malignant non-Hodgkin's lymphomas were reclassified in a retrospective study according to the New Working Formulation for Clinical Usage of the NCI as compared to the Rappaport and Kiel classifications. The reproducibility for the individual schemes this study was 81% (Rappaport), 79% (Kiel), and 85% (New Working Formulation). In keeping with the results of the NCI international study, all lymphomas were subdivided into 3 prognostic groups: (1) low-grade malignancy (6.0 years median survival); (2) intermediate-grade malignancy (3.5 years median survival); and (3) high-grade malignancy (1.4 years median survival). The NCI-proposed New Working Formulation for Clinical Usage is thus recommended as practical and unprejudicing classification scheme for general application; however, its usefulness as tool for translating one classification scheme into another appears limited.     

Cell proliferation and DNA content in non-Hodgkin's lymphoma. Flow cytometry in relation to lymphoma classification

Flow cytofluorometric (FCF) DNA analysis was performed on specimens from 154 patients with non-Hodgkin's lymphoma (NHL) and correlated to histopathology according to the Rappaport classification and the Working Formulation of NHL for clinical usage (WF). NHL associated with unfavorable prognosis (UP) had significantly higher proportions of cells in S-phase as compared to the favorable prognosis (FP) group. The proportion of S-phase cells also differed significantly between the low-, intermediate-, and high-grade malignancy groups of the WF. Aneuploidy was significantly more frequent in the UP (41%) than in the FP (15%) group. By stepwise discriminant analysis, the S-phase frequency was a stronger discriminator between prognostic groups than DNA content. Classification by discriminant analysis showed that over 90% of the low grade/FP lymphomas were allocated to the good prognosis group by their S-phase and DNA values. Due to the variation in the proportion of S-phase cells in the intermediate grade and high grade, as well as the UP lymphomas, only approximately 50% of the UP and 60% of the high-grade lymphomas were identified as such by this discriminant model, while almost one half of the intermediate-grade lymphomas were allocated to the low-grade group. The results suggest that S-phase analysis can be of value in distinguishing intermediate- and high-grade lymphomas with high and low proportions of proliferating cells, which may be prognostic importance.     

Prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas.

The aim of the present research was to evaluate the prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas. For this purpose a series of 100 consecutive, previously untreated adults with advanced malignant non-Hodgkin's lymphomas was analyzed. The median age of the patients was 54 years; 61 patients were males. Although the number of the various groups considered was limited, a statistically significant difference (p less than 0.001) was found in the median survival of patients with lymphomas of low-grade malignancy (lymphocytic, lymphoplasmacytoid, centrocytic, centroblastic-centrocytic lymphoma) and lymphomas of high-grade malignancy (centroblastic, lymphoblastic, immunoblastic lymphoma). A difference in survival (p less than 0.001) was also observed among the patients with lymphocytic lymphoma and those with centroblastic-centrocytic lymphoma, whereas no significant difference in survival was found between the histological subtypes of high-grade malignant lymphomas. Our observations support the opinion that the Kiel classification is useful in clinical practice to distinguish the histological types with a better prognosis from those with a worse one; in addition this classification appears to be of conceptual value.     

Biologic progression in non-Hodgkin's lymphoma. A flow cytometric study

The nuclear DNA content of 37 primary non-Hodgkin's lymphomas both at presentation and at relapse was determined by flow cytometric analysis from paraffin-embedded tissue to investigate changes in DNA ploidy and S-phase fraction (SPF) during the course of the disease, and their association with survival. The repeat biopsies were done from 5 months to 15 years after the diagnosis. Four low-grade lymphomas according to the Working Formulation transformed into intermediate-grade lymphomas (four of 11, 36%), and four intermediate-grade lymphomas into high-grade lymphomas during the follow-up (four of 16, 25%), and five of these eight transformed lymphomas were fatal within 18 months after relapse. The SPF correlated strongly with poor prognosis if measured either from the primary biopsy (P = 0.008), the first (P = 0.009), or the latest repeat biopsy (P = 0.006). If SPF was greater than or equal to 6% larger in a repeat biopsy than at presentation prognosis was poor; six of nine such patients died from lymphoma within 11 months from recurrence. An increase of greater than or equal to 6% in the SPF was more common in high-grade (four of nine, 44%) and intermediate-grade (four of 16, 25%) lymphomas than in low-grade lymphomas (one of 11, 9%), and it was occasionally (three of nine) associated with a morphologic change. In a few cases a repeat biopsy was diploid despite DNA aneuploidy at presentation. In conclusion, the study provides evidence that not only may low-grade lymphomas transform into higher grade lymphomas, but high-grade lymphomas may also frequently transform into more malignant forms during the course of the disease. The SPF is useful in monitoring the biological behavior of non-Hodgkin's lymphoma, and it appears to give information not obtained by histologic study alone.     

Modification of Kiel and working formulation classifications for improved survival prediction in non-Hodgkin's lymphoma

The total survival of 203 patients with non-Hodgkin's lymphoma (NHL) was analyzed according to the working formulation (WF) and "expanded" Kiel classifications. The original Kiel classification consisting of low grade (LG) and high grade (HG) forms corresponded well to the LG and HG forms of the WF. When an expanded Kiel containing an intermediate grade (IG) composed of the original LG diffuse group was devised, this gave a much better separation of survival of the three grades as compared with the WF where the survival of IG and HG forms were nonsignificantly different. The main reason for this difference was the inclusion of the so-called centroblastic diffuse form in the HG Kiel, but in the IG according to the WF. In a "modified" WF analysis where this histologic entity was placed in the HG subgroup, the three survival curves then gave excellent separation like the expanded Kiel classification. Since the centroblastic diffuse form (and its analogous forms according to other classifications) has a poor prognosis, it is important that it be so recognized and treated accordingly with aggressive therapy. We propose either our expanded Kiel or modified WF classification of the three grade forms as an excellent predictor of survival.     

Prognostic factors in primary gastrointestinal non-Hodgkin's lymphoma. A multivariate analysis, report of 106 cases, and review of the literature

The authors have reviewed 106 cases of primary gastrointestinal non-Hodgkin's lymphoma (GI-NHL) treated at the Institut Gustave-Roussy (IGR), France, between 1975 and 1986. The occurrence was 55 in the stomach, 26 in the small intestine, ten ileocecal, seven in the large intestine, and eight patients had multiple involvement. Patients were clinically staged according to the Ann Arbor staging system using the modification of Musshoff for Stage IIE. All histologic material of the 106 patients were reviewed and graded according to the Working Formulation (WF) and the Kiel classifications. Most patients received combination chemotherapy as part or all of their primary treatment program (95 patients, 90%). Seventy five patients (71%) had a multimodality treatment. The overall 5-year survival rate was 60%. Sixteen variables were tested by univariate analyses for prognostic influence on survival. Of these, only clinical stage (P less than 0.001), the achievement of initial complete remission (CR) (P less than 0.001), erythrocyte sedimentation rate (ESR) (P = 0.01), mesenteric involvement (P = 0.03), and serosal infiltration (P = 0.05) were significant prognostic factors. Important variables were tested by a multivariate analysis using the Cox model taking into account different treatment modalities. Only three variables entered the regression analysis at a significant level: clinical stage (P = 0.02), surgical resection (P = 0.03), and histologic grade (Kiel) (P = 0.04). When the achievement of initial CR was introduced into the model, it was the most significant variable (P less than 0.001) whereas all other variables became nonsignificant except for the histologic grade (Kiel) (P = 0.004). Based on results of the multivariate analyses we propose two prognostic classifications of patients: one at the initial evaluation depending on clinical stage, surgical resectability, and histologic grade (Kiel); the other at the end of primary treatment depending on the achievement or not of CR and the histologic grade.     

B-cell lymphomas of high-grade malignancy frequently lack HLA-DR, -DP and -DQ antigens and associated invariant chain

The expression of HLA-DR, HLA-DP and HLA-DQ antigens was studied in an unselected series of 66 B-cell lymphomas by means of immunohistology using monoclonal antibodies against non-polymorphic determinants in a sensitive immunoperoxidase technique. In addition, the expression of the MHC class-II antigen-associated invariant chain (li) was examined. The tumors were classified according to the Kiel classification, 30 being of high-grade and 36 being of low-grade malignancy. Only 6 lymphomas of high-grade and 16 lymphomas of low-grade malignancy showed coordinate strong expression of all HLA class-II antigens and invariant chain as observed in the normal peripheral B cell. Six further tumors of high-grade and 8 tumors of low-grade malignancy contained tumor-cell subsets with reduced expression of one or several of the antigens. Eighteen lymphomas of high-grade and 12 lymphomas of low-grade malignancy contained varying tumor-cell subsets that were negative for HLA-DR, -DP, -DQ and li in a selective or combined manner. Three highly malignant tumors were devoid of all class-II antigens and li; 2 highly malignant tumors expressed invariant chain only. The presence of high-grade malignancy was significantly correlated with the occurrence of tumor cells lacking HLA-DR (p = 0.004), HLA-DP (p = 0.013), HLA-DQ (p = 0.007) or li (p = 0.024).     

Non-Hodgkin's malignant lymphoma with primary gastro-intestinal localisation. Therapeutic aspects

A retrospective analysis of 38 patients with primary gastrointestinal non Hodgkin's lymphoma (PGINHL) referred to "Center Oscar Lambret, Lille, France", from January 1964 to December 1986 has been carried out. Kiel classification and the working formulation for clinical usage were used for histologic diagnosis and Ann Arbor classification modified by Musshoff for clinical staging. The patients, 29 males and 9 females, ranged in age from 7 to 71 years with a mean of 45.5 years for men and 45.1 years for women. Seventeen patients were classified as presenting with low-grade malignancy lymphomas and 21 as high-grade malignancy lymphomas. Nineteen patients presented with early clinical forms and 19 with advanced ones. Laparotomy was performed on all patients but one. Treatment modalities included: surgical resection, chemotherapy and radiotherapy in various combinations. There were 21 patients with recurrence, 6 of them responding to retreatment. The complete population survival curve reached a plateau at 48% after a 41-month follow-up. Five-year survival was 16% for early clinical forms and 80% for advanced ones (P less than 0.001) and 24% for high-grade malignancy lymphomas versus 75% for low-grade malignancy lymphomas (P less than 0.01). Moreover, the 5-year survival rate was 82% for patients with complete surgical resection of primary lesions versus 16% for those with incomplete resections (P less than 0.001). Laparotomy seems to play a major role in diagnostic accuracy, although the role of surgery in therapeutic management remains controversial. However our findings show that surgical resection is important to achieve local control of PGINHL. According to our results the only prognostic determinant that keeps its prognostic value is the extent of surgical resection (complete or incomplete) (P less than 0.05).     

Primary non-Hodgkin's lymphoma of bone: a clinicopathological investigation of 60 cases.

A retrospective analysis of patients presenting with primary lymphoma of bone (PLB) was performed to determine clinical factors affecting prognosis in relation to histological subtype and treatment outcome. Data from 106 patients, presenting with a PLB between 1943 and 1996, were retrieved from the files of the Netherlands Committee on Bone Tumours and Leiden University Medical Centre. The lymphomas were reclassified according to the REAL and updated Kiel classification. The clinical presentation, survival and prognostic factors were investigated. Sixty patients had sufficient clinical information and adequate follow-up to be included in the study. All 33 PLB that could be immunophenotyped were of B cell origin. According to the REAL classification, most PLB were large (B) cell lymphomas (92%) and according to the Kiel classification 45% of the tumours were centroblastic multilobated. PLB presented most often in the long bones (48%), with Ann Arbor stage I (46%), II (16%), IV (16%) and unknown (20%). Stage IV disease was exclusively caused by the presence of multiple bone lesions. Notwithstanding the heterogeneous treatment, the 5-year overall survival was 61%; 46% of patients were progression free at 5 years. Patients at presentation older than 60 had a worse overall survival (76% vs 37%, P = 0.0002) and a worse progression-free period (58% vs 28%, P = 0.0073). Patients with the immunoblastic subtype had a worse survival than the centroblastic mono/polymorphic subtype or the centroblastic multilobated subtype (P = 0.015). Primary lymphoma of bone represents an uncommon bone tumour with a relatively homogeneous morphology and clinical behaviour. Compared to other aggressive lymphomas, PLB have a favourable prognosis.     

Growth fractions in malignant non-Hodgkin's lymphomas (NHL) as determined in situ with the monoclonal antibody Ki-67

The proportion of proliferating cells in malignant non-Hodgkin's lymphomas (NHL) was determined in situ by immunostaining with the monoclonal antibody Ki-67, which reacts with a nuclear antigen that is present only in proliferating cells. A highly significant correlation could be demonstrated between the proportion of Ki-67 positive cells and the classification into high and low-grade NHL according to the Kiel classification. 93.8 per cent of high-grade and 88.5 per cent of low-grade malignancies were correctly allocated to these groups using the percentage of Ki-67 positive cells as discriminant parameter. On the basis of the medians, the degree of proliferation also paralleled the succession of entities within the Kiel classification. Within most of these different entities, however, the ranges of Ki-67 positive cells varied considerably, indicating that the growth fractions within these groups are rather heterogeneous. Thus it might be useful to determine the growth fraction of each individual case of NHL, because this might be of prognostic value.     

Proliferating cell nuclear antigen (PCNA) as a prognostic factor in non-Hodgkin's lymphoma.

The prognostic value of immunoperoxidase staining for proliferating cell nuclear antigen (PCNA) was studied in a series of 140 non-Hodgkin's lymphomas with median follow-up of 9 years. Lymphomas where > 50% of cells showed positive staining for PCNA had inferior 5-year survival as compared with those with less than 50% of positive cells (57% vs 41%, P = 0.008). The presence of > 50% of positively staining cells for PCNA was strongly associated with a larger than the median size of the SPF (median, 8.3%), and high histological grade of malignancy (P < 0.0001 for both). Lymphomas with both a large percentage (> 50%) of PCNA positive cells and a larger than the median SPF had inferior outcome as compared with lymphomas where either one or both of these factors were small. Although PCNA staining was not an independent prognostic factor in a multivariate analysis, it appears to be supplementary to the SPF even if determined from old paraffin-embedded tissue material.     

Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. Classification

Background: One hundred sixty-eight peripheral T-cell lymphomas (PTCLs)were reviewed according to the Revised European–American Lymphoma (R.E.A.L.)Classification.Patients and methods: The cases, originally diagnosed on the basis of theUpdated Kiel Classification (UKC), were all provided with histologicalpreparations, immunophenotype, clinical information, and follow-up data. Theslides were reclassified by five observers, who integrated the R.E.A.Lcriteria with cell size measurements. The prognostic value of clinical andpathologic findings was assessed by univariate and multivariate analysis.Results: The R.E.A.L. Classification was reproducibly applied by all of theobservers. Clinically, anaplastic large cell lymphomas (ALCLs) differed fromthe remaining PTCLs by mean age (29.5 vs. 52.9 years), bulky disease(52.3% vs. 11.3%; P = 0.000), mediastinal mass (52.7% vs.32%; P = 0.004), and disease-free survival (68.0% vs.38.2%; P = 0.0001). Although each histological type displayed specificclinical aspects, PTCLs other than ALCL were basically characterised by a poorclinical outcome which was not influenced by the UKC malignancy grade. Atmultivariate analysis, the risk of a lower complete remission rate was relatedto bulky disease (P = 0.001), histologic group (non-ALCL) (P = 0.01), andadvanced stage (III–IV) (P = 0.0002).Conclusions: The present study supports the classification of T-celllymphomas proposed by the R.E.A.L. scheme.     

Classic prognostic factors, flow cytometric data, nuclear morphometric variables and mitotic indexes as predictors in transitional cell bladder cancer

One hundred and eighty-seven patients with a transitional cell bladder cancer were followed by retrospectively for a mean of 9.5 years. Clinical stage (p less than 0.0001), histological grade (p less than 0.0001), papillary (p less than 0.0001), SPF (p less than 0.0001), M/V index (p less than 0.0001), MAI (p less than 0.0001), DNA index (p = 0.0001) SDNA (p = 0.0004), NA10 (p = 0.0023), NA (p = 0.0044) and G2% (p = 0.0158) were significantly correlated with survival in univariate analysis. In Cox's analysis T-category, papillarity and MAI had independent prognostic value and in combination they predicted bladder cancer-related survival significantly (X2 = 117.5, p less than 0.0001). When histological parameters only were analysed, WHO grade, SPF and papillarity were independent predictors and their combined prognostic significance was high (X2 = 76.6, p less than 0.0001). In papillary tumours SPF (p v 0.0005), MAI (p = 0.0009), DNA index (p = 0.0010) and M/V index (p = 0.0021) predicted survival significantly in addition to stage (P less than 0.0001) and grade (p = 0.0003) in univariate analysis. In Cox's analysis T-category, MAI and M/V index were independent predictors and their combined prognostic value was high (X2 = 54.1, p less than 0.0001). In Ta-T1 and in T2-T3 tumours, WHO grade, papillarity, SPF, mitotic indexes and DI were significant predictors in univariate analysis. In Cox's analysis of Ta-T1 tumours papillarity had independent prognostic value, whereas in papillary Ta-T1 tumours mitotic activity included all prognostic information. In T2-T3 tumours WHO grade and SPF were independent predictors. In conclusion, in papillary bladder tumours T-category is the most important predictor of survival followed by parameters reflecting proliferative activity of cancer cells.     

Comparative analysis of [3H]-thymidine labelling index and monoclonal antibody Ki-67 in non-Hodgkin's lymphomas

The relation between the [³H]-thymidine labelling index (3H-Thy LI), which evaluates the S-phase cells, and the monoclonal antibody Ki-67 (MoAb Ki-67), which recognizes a nuclear antigen expressed during the cell cycle, was defined in 35 non-Hodgkin's lymphomas (NHL). Significantly higher median values of [³H]-Thy LI and Ki-67-positive cells were observed for high-grade than for low-grade malignancy tumours according to the Kiel classification, but with wide and overlapping values for the two morphologic subgroups. A significant correlation was observed between [³H]-Thy LI and Ki-67-positive cells (P < 0.0001; r = 0.62). However, the ratio between the two cell kinetic variables on individual tumours was not constant. It sharply increased with decreasing [³H]-Thy LI values and was much higher in low-grade NHL than in high-grade NHL. Follow-up studies are needed to establish the role of the tumour growth fraction as evaluated by MoAb Ki-67 as a prognostic indicator in NHL.