Comparison of liquid based cytology and histology for the evaluation of HER-2 status using immunostaining and CISH in breast carcinoma

BACKGROUND: HER-2 amplification is an important prognostic biomarker and treatment determinant in breast carcinoma. AIMS: To correlate immunocytochemical (ICC) expression of HER-2 and gene amplification determined by chromogenic in situ hybridisation (CISH) using liquid based cytology (LBC) with immunohistochemistry (IHC) and CISH using histological samples of the same breast carcinomas. METHODS: Frozen sections and cytobrushings of 103 breast carcinomas were analysed. Four techniques were performed on each tumour: two on LBC samples (ICC, and CISH, both graded as positive, indeterminate, or negative) and two on histological samples (IHC and CISH). Two cell lines (MCF-7, negative; BT 474, positive) were used as controls for cytological analysis. A complementary fluorescence in situ hybridisation technique was carried out in histological samples with low amplification (4-10 dots/nucleus). RESULTS: Interobserver agreement for the four techniques calculated by the kappa coefficient indicated a substantial agreement. Nine cases failed in cytology because of poor cellularity. Among 94 cases, 19 were amplified; 73, 12, and 9 tumours were scored 0 or 1+, 2+, and 3+, respectively by IHC and 75, 13, and 6, respectively, by ICC. CISH found no amplification in 72 tumours. Correlations between the IHC and CISH results in the histological and cytological samples were always significant. CONCLUSIONS: Her-2 status could be determined in LBC samples and correlated well with reference histological methods using in situ hybridisation. ICC was less reliable because of the presence of the cytoplasmic membrane. However, these results should be confirmed by a large multicentre study.     

Incidence of inhibitor development in a group of young hemophilia A patients treated exclusively with lyophilized cryoprecipitate

The incidence of neutralizing isoantibody formation to infused factor VIII in a cohort of 67 hemophilia A patients, born between January 1, 1971 and April 30, 1990, who had been treated exclusively with lyophilized cryoprecipitate, was 6% (5.3 per 1,000 patient years of observation). The age-dependent cumulative risk was 4.6% at 4 years of age and 6.7% at 8 years of age. Recent reports in patients treated with a variety of more pure concentrates show a much higher incidence of inhibitor formation and tend to be used as a reference when new concentrates are introduced. We believe that a patient group, such as the one studied here, is a more suitable reference population because these patients have been exclusively treated with a single factor VIII preparation.     

Phase I trial with recombinant human interleukin-3 in patients with lymphoma undergoing autologous bone marrow transplantation

Recombinant human interleukin-3 (rhIL-3) was administered to 30 patients undergoing autologous bone marrow transplant (ABMT) for treatment of lymphoma. In this phase I dose escalation study, rhIL-3 was administered from day 0 to 20 after ABMT by 2-hour intravenous infusion at dose levels of 1, 2, 5, and 10 micrograms/kg/d. Seventeen patients did not complete therapy with rhIL-3. Eleven requested early discontinuation for malaise, confusion, transplant complications, or rapid engraftment and were removed from the study, whereas six patients developed grade III toxicity, including fever (three patients), or headache (three patients) possibly attributable to rhIL3. Other common toxicities included diarrhea, rigors, mucositis, and rash. The maximum tolerated dose of rhIL-3 was 2 micrograms/kg/d. No evidence of earlier hematopoietic cell recovery was observed compared with similar historical patients treated with recombinant human granulocyte- macrophage colony-stimulating factor. Future trials will be needed to determine alternate schedules of administration of rhIL-3 or the use of rhIL-3 in combination or in sequence with other growth factors.     

Immune human lymphocytes produce an acid-labile α-interferon

We have described in this paper a novel human interferon (IFN) with antigenic and cross-species reactivity of α-IFN and physicochemical properties of γ-IFN. This IFN is produced by normal peripheral blood mononuclear cells during an immune response but has also been associated with autoimmune disease (10). The system described here will be useful in elucidating the biological significance and cell of origin of this IFN.     

P16 is overexpressed in cutaneous carcinomas located on sun-exposed areas

BACKGROUND: Recently, an increased expression of P16, a cell cycle regulatory tumor suppressor protein, has been demonstrated in cervical squamous neoplasms as a marker of malignancy. In contrast, studies performed in skin carcinomas led to contradictory results. OBJECTIVES: Our first aim was to evaluate P16 expression in different types of non-melanoma skin cancers compared with normal skin and benign tumors. The second aim was to evaluate the relationship between P16 expression and the location of skin tumors (i.e. exposed versus non exposed sites). Finally, we also studied Ki67 expression in skin carcinomas and control biopsies. METHODS: Skin biopsy specimens with typical histologic features of squamous cell carcinoma (SCC; n = 30), Bowen's disease (BD; n = 17), basal cell carcinoma (BCC; n = 10), seborrheic keratosis (SK; n = 10) and normal human skin (NHS; n = 9) were obtained from 76 patients seen at our institution between 2001 and 2003. In all cases, P16 and Ki67 expression were evaluated by immunohistochemistry and image analysis. RESULTS: P16 overexpression was observed in 58% of cutaneous carcinomas (SCC: 60%; BD: 58%; BCC: 50%) versus 0% of SK or NHS (0%) (p = 0.006). Ki67 expression in over 5% of tumour cells was observed in 69% of cutaneous carcinomas (SCC: 54%; BD: 76%; BCC: 80%) versus 16% in the group including SK (30%) and NHS (0%) (p = 0.04). Overexpression of P16 was associated with a high rate of Ki67 positive tumour cells in 23/57 malignant skin tumors (40%). Both P16 was associated and Ki-67 were negative in 7/57 cases (12%). Sixty-eight percent of tumors located on sun-exposed areas versus 23% of those located on non sun-exposed areas overexpressed P16 (p = 0.02). CONCLUSION: Our study demonstrated that the expression of P16 and Ki67 is associated with skin carcinomas. No difference was observed according to histological types of carcinomas, suggesting that P16 and Ki67 expression did not correlate with the degree of proliferation and malignancy. Within cutaneous carcinoma specimens, P16 overexpression was significantly associated with the location on sun-exposed areas, suggesting a possible induction of P16 overexpression by UV radiation.