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Giancarlo Pruneri

Publications and source records attributed to Giancarlo Pruneri.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic factors affecting survival after surgical resection of gastrointestinal stromal tumours: a two-unit experience over 10 years.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) tract which has only been recently described based on their specific immunohistochemistry and the presence of particular KIT-related mutations which potentially make them targets for tyrosine kinase inhibition. METHODS: Sixty-one patients (29 M; 32 F, median age 60 years; range: 23-86 years) between June 1994 and March 2005, were analyzed from two allied institutions. Patient, tumour, and treatment variables were analyzed to identify factors affecting survival. RESULTS: Of the 61 patients, 55 (90%) underwent complete surgical resection of macroscopic disease. The 5-year overall survival (OS) rate in the 61 patients was 88% and the 5-year disease-free survival (DFS) in the 55 cases completely resected was 75%. Univariate analysis revealed that R0 resection was strongly associated with a better OSrate (p < 0.0001). Likewise, univariate analysis also showed high mitotic count of > 10 mitoses/per 50 HPF was a significant variable in worse prognosis for OS ( 10 mitoses/per 50 HPF 74% 5-year OS, respectively; p = 0.013). On subsequent multivariate analysis, only high mitotic count remained as a significant negative prognostic variable for OS (p = 0.029). Among patients resected for cure, there were 8 recurrences during follow-up. The mean time to recurrence was 21 +/- 10 months (range: 4-36 months). Univariate analysis revealed that mitotic count of > 10 mitoses per 50 high power fields, intratumoural necrosis, and pathological tumour size (> 10 cm in maximal diameter) significantly correlated with DFS (p = 0.006, 0.002 and 0.02, respectively), with tumour necrosis and high mitotic count remaining as independent predictive variables affecting prognosis on subsequent multivariate analysis. CONCLUSION: Most GISTs are resectable with survival principally dependent upon mitotic count and completeness of resection. Future metabolic and genetic analyses will define the role of and resistance to induction or postoperative adjuvant targeted kinase inhibition therapy.

Journal Article↗
PubMed2006

Surgical outcomes after total mesorectal excision for rectal cancer.

BACKGROUND AND OBJECTIVES: This study reviewed the results of surgery for distal rectal cancer following the introduction of total mesorectal excision (TME) for rectal cancer. METHODS: Two hundred sixty-four patients who had undergone elective curative surgical resection of rectal cancer within 12 cm of the anal verge were included. Comparisons were made between patients who had different surgical procedures. RESULTS: The overall operative mortality rate was nil, and the morbidity 39.4%. With a mean follow-up of 34 months (range 5-105 months), local recurrence occurred in 21 of the patients. The 3- and 5-year actuarial local recurrence rates were 9% and 12%, respectively for the whole group. Abdominoperineal resection (APR) was necessary in 65 of 264 (24.6%) of the patients, with a very low local recurrence rate in this subgroup (5% at 3 years). On multivariate analysis, only stage was a significant prognosticator of overall survival (P = 0.012). CONCLUSIONS: With the practice of TME, APR was still necessary in 25% of patients with rectal cancer within 12 cm of the anal verge. Type of surgery and tumor distance from the anal verge influenced local recurrence rates, but only initial tumor stage was associated with long-term survival.

Adult↗
PubMed2006

Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy.

Antiangiogenic agents and therapeutic strategies have entered the clinical oncology arena. The classical tumor size measurements defined to monitor efficacy of chemotherapy, however, might not be appropriate for these newer therapeutics. We previously found that circulating endothelial cells (CECs) were increased in number and more viable in cancer patients compared with control subjects. We investigated the correlation between CEC kinetics and clinical outcome in patients with advanced breast cancer receiving metronomic chemotherapy, a therapeutic strategy associated with antiangiogenic activity and anticancer efficacy. CEC number and viability were measured by flow cytometry in patients and in preclinical models. CECs were decreased in patients for whom no overall clinical benefit (defined as a clinical response or a stable disease) was observed compared with those who had a clinical benefit (P = .015). This difference was due to an increased fraction of apoptotic CECs in patients with a clinical benefit. Univariate and multivariate analyses indicated that CEC values greater than 11/microL were associated with a longer progression-free survival (P = .001) and an improved overall survival (P = .005). Preclinical models indicated that the source of apoptotic CECs was most likely the tumor vasculature. CEC kinetics and viability are very promising as predictors of clinical response in patients undergoing metronomic chemotherapy.

Adult↗
PubMed2006

Delocalization and destabilization of the Arf tumor suppressor by the leukemia-associated NPM mutant.

One third of acute myeloid leukemias (AMLs) are characterized by the aberrant cytoplasmic localization of nucleophosmin (NPM) due to mutations within its putative nucleolar localization signal. NPM mutations are mutually exclusive with major AML-associated chromosome rearrangements and are frequently associated with a normal karyotype, suggesting that they are critical during leukemogenesis. The underlying molecular mechanisms are, however, unknown. NPM is a nucleocytoplasmic shuttling protein that has been implicated in several cellular processes, including ribosome biogenesis, centrosome duplication, cell cycle progression, and stress response. It has been recently shown that NPM is required for the stabilization and proper nucleolar localization of the tumor suppressor p19(Arf). We report here that the AML-associated NPM mutant localizes mainly in the cytoplasm due to an alteration of its nucleus-cytoplasmic shuttling equilibrium, forms a direct complex with p19(Arf), but is unable to protect it from degradation. Consequently, cells or leukemic blasts expressing the NPM mutant have low levels of cytoplasmic Arf. Furthermore, we show that expression of the NPM mutant reduces the ability of Arf to initiate a p53 response and to induce cell cycle arrest. Inactivation of p19(Arf), a key regulator of the p53-dependent cellular response to oncogene expression, might therefore contribute to leukemogenesis in AMLs with mutated NPM.

Acute Disease↗
PubMed2006

Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.

Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.

Apoptosis↗
PubMed2006

Comparative genome-wide profiling of post-transplant lymphoproliferative disorders and diffuse large B-cell lymphomas.

Post-transplant lymphoproliferative disorders (PTLD) are a major complication of solid organ transplantation, representing a cause of severe morbidity and mortality. Apart from Epstein-Barr virus infection, knowledge of the pathogenesis of monoclonal PTLD is limited. Powerful analysis techniques, such as whole genomic DNA profiling (array comparative genomic hybridisation), can improve our understanding of PTLD pathogenesis. Whole genome profiling using the Affymetrix GeneChip Human Mapping 10 k 2.0 was performed on 20 PTLD cases and 25 cases of diffuse large B-cell lymphoma (DLBCL) from immunocompetent patients as a control group. Recurrent lesions were detected among all the samples. Chromosome 18q, 7q, 3q and 12 were the most common gains in the control group. Chromosomes 5p and 11p were commonly gained in PTLD-DLBCL. The latter had frequent losses of 6q, 17p, 1p and 9p. Chromosome 12p was the most frequent target of deletions among PTLD-DLBCL cases. Loss of heterozygosity (LOH) did not always match DNA loss: chromosome 10 seemed to be targeted by uniparental disomy in PTLD. Small deletions and gains, involving both known (BCL2 and PAX5) and unknown genes (ZDHHC14), were identified. These data suggest that PTLD share, at a lower frequency, common genetic aberrations with DLBCL from immunocompetent patients. The demonstration of 9p13 amplification emphasises the importance of PAX5 in PTLD. The combination of DNA copy number and LOH assessment lead to the hypothesis that uniparental disomy may be a potential mechanism in B-cell lymphomagenesis.

Chromosome Aberrations↗
PubMed2006

Effect of resection and outcome in patients with retroperitoneal sarcoma.

BACKGROUND: A consecutive series of 47 patients with retroperitoneal sarcoma (RPS) were resected and prospectively followed. METHOD: Between July 1994 and March 2005, 47 patients (24 men, 23 women; mean age, 56 years; range, 17-82 years) were evaluated. RESULTS: A total of 23 patients had primary RPS and 24 patients had recurrent RPS. A total of 30 out of 47 patients (64%) underwent removal of contiguous intra-abdominal organs. The peroperative mortality was nil and significant preoperative complications occurred in eight cases only (17%). High tumour grade and incomplete resection were significant variables for a worse survival in all 47 patients, both in the univariate and multivariate analyses (P = 0.008 and P = 0.016, respectively). Among 28 radically resected patients, only histological grade affected overall survival (90% 5-year survival for low-grade tumour vs 26% 5-year survival for high-grade tumour; P = 0.006) with a similar effect noted for disease-free survival. CONCLUSIONS: Histological grade was the only factor that affected overall and disease-free survival for RPS tumours. An aggressive surgical approach in both primary and recurrent RPS is associated with long-term survival.

Adolescent↗
PubMed2005

Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma.

Multiple myeloma (MM) is the most common form of plasma cell dyscrasia, characterized by a marked heterogeneity of genetic lesions and clinical course. It may develop from a premalignant condition (monoclonal gammopathy of undetermined significance, MGUS) or progress from intramedullary to extramedullary forms (plasma cell leukemia, PCL). To provide insights into the molecular characterization of plasma cell dyscrasias and to investigate the contribution of specific genetic lesions to the biological and clinical heterogeneity of MM, we analysed the gene expression profiles of plasma cells isolated from seven MGUS, 39 MM and six PCL patients by means of DNA microarrays. MMs resulted highly heterogeneous at transcriptional level, whereas the differential expression of genes mainly involved in DNA metabolism and proliferation distinguished MGUS from PCLs and the majority of MM cases. The clustering of MM patients was mainly driven by the presence of the most recurrent translocations involving the immunoglobulin heavy-chain locus. Distinct gene expression patterns have been found to be associated with different lesions: the overexpression of CCND2 and genes involved in cell adhesion pathways was observed in cases with deregulated MAF and MAFB, whereas genes upregulated in cases with the t(4;14) showed apoptosis-related functions. The peculiar finding in patients with the t(11;14) was the downregulation of the alpha-subunit of the IL-6 receptor. In addition, we identified a set of cancer germline antigens specifically expressed in a subgroup of MM patients characterized by an aggressive clinical evolution, a finding that could have implications for patient classification and immunotherapy.

Adult↗
PubMed2005

Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement.

BACKGROUND: Overt ipsilateral axillary lymph node metastases of breast cancer are the most significant prognostic indicators for women who have undergone surgery, yet the clinical relevance of minimal involvement (isolated tumor cells and micrometastases) of these nodes is uncertain. PATIENTS AND METHODS: We evaluated biologic features, adjuvant treatment recommendations, and prognosis for 1,959 consecutive patients with pT1-3, pN0, minimal lymph node involvement (pN1mi or pN0i+), or pN1a (single positive node) and M0, who were operated on and counseled for medical therapy from April 1997 to December 2000. RESULTS: Patients with pN1a and pN1mi/pN0i+, when compared with patients with pN0 disease, were more often prescribed anthracycline-containing chemotherapy (39.1% v 33.2% v 6.1%, respectively; P < .0001) and were less likely to receive endocrine therapy alone (9.8% v 19.4% v 41.9%, respectively; P < .0001). At the multivariate analysis, a statistically significant difference in disease-free survival (DFS) and in the risk of distant metastases was observed for patients with pN1a versus pN0 disease (hazard ratio [HR] = 2.04; 95% CI, 1.46 to 2.86; P < .0001 for DFS; HR = 2.32; 95% CI, 1.42 to 3.80; P = .0007 for distant metastases) and for patients with pN1mi/pN0i+ versus pN0 disease (HR = 1.58; 95% CI, 1.01 to 2.47; P = .047 for DFS; HR = 1.94; 95% CI, 1.04 to 3.64; P = .037 for distant metastases). CONCLUSION: Even minimal involvement of a single axillary node in breast cancer significantly correlates with worse prognosis compared with no axillary node involvement. Further studies are required before widespread modification of clinical practice.

Adult↗
PubMed2005

Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution.

BACKGROUND: Reliable predictors of metastatic involvement would enable a better selection of candidate patients for sentinel lymph node biopsy (SLNB) and possibly allow identification of patients with such a low risk of axillary sentinel lymph node (SLN) involvement to be even spared SLNB. METHODS: The authors evaluated 4351 consecutive patients surgically treated for breast carcinoma who also underwent SLNB. Clinicopathologic features significantly associated with SLN metastases by univariate analysis were included in a multivariate model. RESULTS: By multivariate analysis, the prevalence of SLN metastases was associated directly with tumor size, multifocality, and with the occurrence of peritumoral vascular invasion (PVI; all P < 0.0001), and was associated inversely with a favorable histotype (P = 0.0007) and lack of progesterone receptors (P = 0.004). A predictive model based on the features more closely associated with SLN status documented that the patients with a favorable tumor type </= 1 cm in size and without PVI (n = 178 [4% of the population]) had the lowest risk of SLN metastases (9.5%) whereas patients with tumors > 2 cm and with PVI (n = 250 [5.7% of the population]) had the highest risk (77.2%) of SLN involvement. CONCLUSIONS: Tumor size and PVI emerged as the most powerful independent predictors of SLN metastases. Although no combination of features identified patients with a < 9.5% risk of SLN metastases, the current data may be used to tailor the management of patients with breast carcinoma with the aim of minimizing as much as possible the diagnostic and therapeutic procedures, thus improving the quality of life of the patients without any adverse effect on their survival rates.

Adolescent↗
PubMed2005

Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy.

PURPOSE: Preliminary results using rituximab in extranodal marginal zone (MALT) non-Hodgkin's lymphoma (NHL) patients seem to indicate a relevant clinical activity. Aim of the present study is to investigate the efficacy of conventional weekly treatment using rituximab in gastric MALT NHL patients resistant/refractory or not suitable for eradication treatment, and to evaluate the relevance of the t(11; 18)(q21; q21) translocation and its possible role as a predictive criteria of response. PATIENTS AND METHODS: Twenty-seven patients presenting with gastric MALT NHL at any stage, relapsed/refractory to initial treatment or not suitable for eradication were treated with rituximab in a weekly conventional schedule and evaluated for response and relapse. Flourescence in situ hybridization (FISH) analysis for the presence of 18q21 translocation was performed in 21 patients and was evaluated with clinical outcome. RESULTS: Among the 26 evaluated patients, 20 (77%) achieved an objective response. Twelve patients (46%) had a pathological and clinical complete remission, and eight (31%) had a partial response. With a median follow-up of 33 months, only two patients relapsed at 26 and 14 months, respectively. No correlation was founded between FISH analysis and response or relapse. CONCLUSION: Our experience seems to confirm the clinical activity of rituximab in gastric MALT NHL patients resistant/refractory to antibiotics treatment or not presenting with clinical evidence of Helicobacter pylori infection. The t(11; 18)(q21; q21) translocation seems not to be a predictive marker to response or to subsequent relapse.

Adult↗
PubMed2005

Cyclin D3 immunoreactivity is an independent predictor of survival in laryngeal squamous cell carcinoma.

PURPOSE: To analyze the prevalence and clinical relevance of cyclin D3 abnormalities in laryngeal squamous cell carcinoma (LSCC). EXPERIMENTAL DESIGN: Cyclin D3 immunoreactivity was evaluated in 223 formalin-fixed and paraffin-embedded samples of LSCC patients with a mean follow-up of 62.8 +/- 43.2 months. The occurrence of cyclin D3 extra signals was analyzed by fluorescence in situ hybridization in 47 randomly selected cases collected in a tissue microarray. Cyclin D1 immunoreactivity had been previously investigated in 133 cases. RESULTS: Cyclin D3 immunoreactivity and gene extra signals were found in 39.5% and 42.6% of the cases, respectively, and the concordance between immunohistochemical and fluorescence in situ hybridization results was 70.2% (P = 0.0085). Cyclin D3 immunoreactivity was significantly associated with a high risk of death. Multivariate analysis showed that high tumor grade, exophytic/ulcerating tumor type, low performance status, and cyclin D3 immunoreactivity were the only independent predictors of poor overall survival. In the 133 cases analyzed for both cyclin D1 and cyclin D3, patients with cyclin D1+/cyclin D3+ tumors experienced the worst prognosis, patients with cyclin D1-/cyclin D3- exhibited the most prolonged survival, and with cyclin D1-/cyclin D3+ or cyclin D1+/cyclin D3- tumors an intermediate course was associated. CONCLUSIONS: Our data suggest that cyclin D3 immunoreactivity, possibly due to the occurrence of gene extra copies, may represent an adjunct in LSCC patients' prognostication and contribute to identify D-type cyclins as potential targets of newly developed therapies.

Adult↗
PubMed2005

The transactivating isoforms of p63 are overexpressed in high-grade follicular lymphomas independent of the occurrence of p63 gene amplification.

p63 is a p53-related gene mapping to 3q28 that codes for multiple mRNA transcripts with (TA-p63) or without (DeltaN-p63) transactivating effects on genes that promote cell differentiation and apoptosis. We analysed p63 alterations by immunohistochemistry, quantitative real-time RT-PCR and FISH in a series of 45 follicular lymphomas (FL). None of the tumours showed immunoreactivity for the p40 antibody, which recognizes only the truncated isoforms of p63, or DeltaN-p63 mRNA expression. Immunoreactivity for the 4A4 antibody, which recognizes both the transactivating and the truncated p63 isoforms, was found in 5 +/- 5.5%, 6.85 +/- 4.88% and 33.2 +/- 22.31% of grade I, II and III FL cells, respectively (p < 0.0001). Quantitative RT-PCR analysis showed that all cases but one had TA-p63 mRNA levels higher than non-neoplastic lymphocytes, and that TA-p63 mRNA expression correlated significantly (r = 0.9194, p < 0.0001) with the prevalence of p63 immunoreactivity. FISH extra signals for the p63 gene were found in seven (23.3%) of the 30 cases analysed (0/6 grade I, 2/15 grade II and 5/9 grade III; p = 0.01937). Further hybridizations showed a pattern highly suggestive of chromosome 3 polysomy in six cases. One of these cases also bore extra copies of the p63 and bcl-6 genes. Co-localization of p63 and IgH signals was found in one case. No association between the prevalence of p63 immunoreactivity and extra p63 gene signals was detectable when the cases were dichotomized according to a p63 immunoreactivity threshold of 10%. Our data suggest that TA-p63 is overexpressed in high-grade FL, possibly independent of the occurrence of gene abnormalities, and that it may be involved in the highly complex mechanism of regulation of apoptosis of FL cells.

Adult↗
PubMed2005

Prognostic relevance of CD105+ microvessel density in HNSCC patient outcome.

Angiogenesis is essential for the development and progression of malignant tumours, and there is increasing evidence that microvessel density (MVD) can be considered an indirect marker of neo-angiogenesis. However, there is still disagreement concerning the clinical relevance and prognostic significance of MVD in head and neck squamous cell carcinomas (HNSCCs). MVD was evaluated in 127 HNSCC patients by means of immunohistochemistry using monoclonal antibodies (mAbs) against CD34 and CD105 (endoglin), which has recently been described as a potent marker of neo-vascularisation in various malignancies. MVD was expressed as the mean number of vessels/mm2. The mean CD34+ and CD105+ MVD values were significantly higher in T3-T4 tumours and those in an advanced clinical stage; furthermore, CD105+ MVD was significantly higher in N+ tumours. The patients with a high CD105+ MVD had a significantly shorter disease-free and overall survival; CD34+ MVD was not associated with survival. Similarly, in the subset of lymph-node negative patients, higher CD105+ MVD values were significantly associated with either OS and DFS. Multivariate analysis showed that a high CD105+ MVD was the only independent marker of tumour recurrence or death. Our data suggest that CD105+ MVD may represent an additional prognostic factor in HNSCC patients providing more accurate data for the determination of prognosis and management in the subset of lymph node negative patients.

Adult↗
PubMed2005

Immunoreactivity for c-kit and p63 as an adjunct in the diagnosis of adenoid cystic carcinoma of the breast.

Adenoid cystic carcinoma of the breast represents a unique clinicopathologic entity with a variable histological appearance and a relatively indolent clinical course in most of the cases. Adenoid cystic carcinoma may be difficult to differentiate from infiltrating duct carcinomas, and in particular from tubular and cribriform carcinomas, especially in core or vacuum-assisted biopsies. We evaluated the prevalence of c-kit, p63, and e-cadherin immunoreactivity in a series of 20 adenoid cystic carcinomas, comparing the results with those obtained in a series of infiltrating tubular carcinomas and infiltrating cribriform carcinomas. The hormone receptor status, proliferation labeling index, and HER/2 immunoreactivity had been previously investigated in all the cases. Three (15%) adenoid cystic carcinomas and all infiltrating tubular and cribriform carcinomas showed estrogen receptor and/or progesterone receptor immunoreactivity (P < 0.00001 for estrogen and P = 0.00002 for progesterone receptors). Adenoid cystic carcinomas consistently lacked any immunoreactivity for HER/2, whereas three (15%) infiltrating and cribriform carcinomas showed weak and incomplete membrane staining (P = 0.23077). Membranous immunoreactivity for c-kit was found in all except one (predominantly basaloid) adenoid cystic carcinomas (95%), and in none of the infiltrating tubular and cribriform carcinomas (P < 0.00001). Nuclear immunoreactivity for p63 was found in all except three (predominantly basaloid) adenoid cystic carcinomas (85%) and in none of the infiltrating tubular and cribriform carcinomas (P < 0.00001). All infiltrating tubular and cribriform carcinomas and 18/20 (90%) adenoid cystic carcinomas showed immunoreactivity for e-cadherin (P = 0.48718). In summary, adenoid cystic carcinomas showed the following phenotype: estrogen receptor-/progesterone receptor-/c-kit+/p63+ (13 cases, 65%), estrogen receptor-/progesterone receptor/c-kit+/p63- (three cases, 15%), estrogen receptor-/progesterone receptor-/c-kit-/p63+ (one case, 5%), estrogen receptor+/progesterone receptor+/c-kit+/p63+ (two cases, 10%), and estrogen receptor+/progesterone receptor-/c-kit+/p63+ (one case). By contrast, all the infiltrating tubular and cribriform carcinomas showed the estrogen receptor+/progesterone receptor+/c-kit-/p63- phenotype. Our data provide evidence that immunoreactivity for c-kit and/or p63 may be useful in differentiating adenoid cystic carcinomas from other types of breast cancer.

Adult↗
PubMed2005

SP4, a novel anti-cyclin D1 rabbit monoclonal antibody, is a highly sensitive probe for identifying mantle cell lymphomas bearing the t(11;14)(q13;q32) translocation.

Immunohistochemistry is the most widely used approach in the diagnosis of mantle cell lymphoma (MCL). However, its reliability may be hampered by several technical reasons, necessitating the use of alternative techniques such as the identification of the t(11;14)(q13;q32) translocation to characterize such lesions. The authors compared two monoclonal antibodies (DCS-6 and SP4) for assessing cyclin D1 immunoreactivity in a series of 22 MCLs. Their results documented that SP4, a novel rabbit monoclonal antibody, is more effective than the mouse monoclonal antibody DCS-6, one of the most commonly used reagents in daily practice. Although DCS-6 and SP4 were capable of identifying cyclin D1 immunoreactivity in 95.4% and 100% of the cases analyzed, respectively, the prevalence of cyclin D1 immunoreactive neoplastic cells was significantly (P < 0.0001) higher with SP4 (86.6 +/- 13.1%) than with DCS-6 (39.8 +/- 32%). Moreover, the staining intensity was faint in 16 (76.2%) cases and moderate to strong in 5 (23.8%) cases immunostained with DCS- 6, while all the cases showed a moderate to strong immunoreactivity with SP4 (P < 0.0001). According to an arbitrary score based on the percentage of immunoreactive neoplastic cells and staining intensity, only 10 (45.4%) cases were considered high cyclin D1 expressors after staining with DCS-6, whereas all the cases were high expressors with SP4 (P < 0.0001). These data provide evidence that the SP4 monoclonal antibody may be a fast, easy-to-interpret, and reliable surrogate for the detection of the (11;14) translocation by molecular techniques.

Animals↗
PubMed2005

Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy.

OBJECTIVE: To assess whether the risk for nonsentinel node metastases may be predicted, thus sparing a subgroup of patients with breast carcinoma and a positive sentinel lymph node (SLN) biopsy completion axillary lymph node dissection (ALND). SUMMARY BACKGROUND DATA: The SLN is the only involved axillary lymph node in the majority of the patients undergoing ALND for a positive SLN biopsy. A model to predict the status of nonsentinel axillary lymph nodes could help tailor surgical therapy to those patients most likely to benefit from completion ALND. METHODS: All the axillary sentinel and nonsentinel lymph nodes of 1228 patients were reviewed histologically and reclassified according to the current TNM classification of malignant tumors as bearing isolated tumor cells only, micrometastases, or (macro)metastases. The prevalence of metastases in nonsentinel lymph nodes was correlated to the type of SLN involvement and the size of the metastasis, the number of affected SLNs, and the prospectively collected clinicopathologic variables of the primary tumors. RESULTS: In multivariate analysis, further axillary involvement was significantly associated with the type and size of SLN metastases, the number of affected SLNs, and the occurrence of peritumoral vascular invasion in the primary tumor. A predictive model based on the characteristics most strongly associated with nonsentinel node metastases was able to identify subgroups of patients at significantly different risk for further axillary involvement. CONCLUSIONS: Patients with the most favorable combination of predictive factors still have no less than 13% risk for nonsentinel lymph node metastases and should be offered completion ALND outside of clinical trials of SLN biopsy without back-up axillary clearing.

Adult↗