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Intrasinusoidal infiltration (ISI) is a pattern of invasion that is rarely found on bone marrow (BM) biopsies, and is considered as a hallmark of splenic marginal zone cell lymphoma (SMZL). We analysed BM biopsies showing intrasinusoidal infiltration from 54 consecutive patients with different types of lymphoma to verify if ISI quantity was a diagnostic criterion for SMZL. There were 35 primary splenic lymphoma (PSL) and 19 non-PSL; 28 SMZL, three non-splenic MZL, six mantle cell, six small lymphocytic, four follicular, four diffuse large B cell, one peripheral T cell, one lymphoplasmacytic and one anaplastic large-cell lymphoma. The quantity of BM infiltrate was assessed on CD45, CD20 and CD3 stained sections. The mean percentage of total (TI) and intrasinusoidal (ISI) lymphocytes was calculated in 10 areas for each case. TI quantity was 21.57 in PSL and 35.05 in non-PSL (P = 0.04). ISI quantity was 5.23 in PSL and 7.62 in non-PSL (P = 0.08), 5.83 in SMZL and 2.83 in other types of PSL (P = 0.12), 4.46 in non-splenic MZL and 8.21 in other types of non-PSL (P = 0.28). No difference in ISI quantity was found among the lymphoma subtypes, either in PSL (P = 0.74) or non-PSL (P = 0.3). The data demonstrate that ISI quantity in BM biopsies is not a reliable diagnostic parameter for SMZL.

The expression of p53, c-erbB-2, bcl-2 and c-myc proteins was compared to the quantity of the nucleolar organiser regions (AgNORs) and MIB-1 antigen to elucidate the relationship between oncogene expression and rapidity of cell proliferation and tumor growth fraction. Sections from 50 male breast carcinomas (MBC) and 62 superficial papillary bladder neoplasias were stained with the standardised AgNOR method and monoclonal antibodies MIB-1, DO7, CB11, bcl-2 124 and 9E11. p53 immunopositivity was associated with high AgNOR quantity and MIB-1 scores both in MBC and bladder neoplasm. c-erbB-2 expression was associated with high AgNOR quantity in bladder neoplasm. bcl-2 expression was associated with low AgNOR quantity in MBC. c-myc expression was associated with high AgNOR quantity in MBC. MBC patients with low AgNOR quantity, and p53, c-erbB-2 and c-myc immunonegativity had the longest overall survival. Patients with bladder neoplasia with low AgNOR quantity, negative p53 and positive c-erbB-2 immunostaining had the longest disease-free survival time. Our results indicate that p53 overexpression reflects both the rapidity of cell proliferation, as assessed by AgNOR quantity, and tumor growth fraction, as assessed by MIB-1 scores, while c-erbB-2, c-myc and bcl-2 expression mainly reflects the rapidity of cell proliferation. The combination of AgNOR quantity and oncogene expression may stratify patients into different risk groups.

BACKGROUND Recurrence of transitional cell carcinoma of the bladder cannot be predicted accurately by traditional criteria alone. This study examined the value of cell proliferative activity, morphometry, and expression of p53, c-erbB-2, and bcl-2 oncogenes in predicting recurrence of superficial papillary urothelial neoplasms of low malignant potential (LMP) and Grade 1 (G1) papillary carcinomas of the bladder. METHODS Sixty-two patients (mean age, 62 years) with newly diagnosed superficial pTa bladder tumors (19 LMP, and 43 G1) were analyzed retrospectively. All patients underwent transurethral resection (TUR). Median follow-up was 69 months. Serial sections from formalin-fixed, paraffin-embedded material at initial TUR were stained with monoclonal antibodies (MoAbs) DO7, CB11, and bcl-2-124. Cell proliferation was assessed by MIB-1 MoAb, the quantity of argyrophilic nucleolar organizer region-associated proteins (AgNORs), and mitotic count. RESULTS Of the 62 patients, 42 (67.7%) had one or more recurrences. Recurrence rates were higher in MIB-1 (P < 0.0001) and p53 immunopositive cases (P = 0.02), when the mitotic count was greater than 5 (P = 0.004), and in G1 carcinomas (P = 0.04). In univariate analysis, the disease-free period was shorter for MIB-1 (P < 0.0001) and p53 immunopositive (P = 0.0001) cases, for cases with high AgNOR quantity (P = 0.04), mitotic count greater than 5 (P = 0.01), and in G1 carcinomas (P = 0.002). In multivariate analysis, only MIB-1 immunoreactivity retained independent prognostic significance. CONCLUSIONS Despite the small cohort, the results confirm the prognostic value of cell proliferation and p53 expression in patients with bladder neoplasms. The results also indicate that MIB-1 immunopositivity is the most significant predictor of recurrence and disease-free survival in superficial LMP and G1 papillary bladder carcinomas. Cancer 2002;95:784–90. © 2002 American Cancer Society. DOI 10.1002/cncr.10733

We investigated the expression of oncogenes p53, c-erbB-2, and bcl-2 and cell proliferative activity in 62 newly diagnosed superficial pTa papillary bladder tumors. Based on the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications, 19 were urothelial neoplasias of low malignant potential (LMP) and 43 low-grade (grade 1) papillary carcinomas. All the patients underwent transurethral resection and were followed up to 97 months; 42 had recurrences. Initial biopsies were tested for p53, c-erbB-2, and bcl-2 proteins using DO7, CB11, and bcl-2 124 monoclonal antibodies. Cell proliferation was assessed by MIB-1 mAb and mitotic count. LMP had significantly lower MIB-1 (p = 0.002) and p53 immunopositivity (p = 0.03), mitotic count (p = 0.006), and recurrence rates (p = 0.04) than did grade 1 cases, whereas no difference was observed for c-erbB-2 and bcl-2 expression. The median disease-free survival for LMP was 76 months but only 15 months for grade 1 cases (p = 0.002). Although the cohort is small, the results indicate that the distinction between LMP and low-grade (grade 1) papillary urothelial neoplasias, as proposed by the 1998 WHO/ISUP and 1999 WHO classifications, reflects different biologic activity and clinical behavior; however, a long-term follow-up is advisable also for patients with LMP.