Occult HIV infection in a large sample of health-care users in Lombardy, Italy in 2014-2015: implications for control strategies.

We estimated the number of people unaware of their human immunodeficiency virus (HIV) infection in our province, Pavia (population 540 000) in Lombardy, Italy, by means of anonymous unlinked testing of 10 044 serum/plasma samples residual from clinical analyses at the outpatient clinic of Policlinico San Matteo in 2014 and 2015. Ethical and legal approval was obtained prior to study start. Samples were irreversibly anonymised, only retaining gender and 5-year age class. Five sample pools were tested for HIV using LIAISON® XL MUREX HIV Ab/Ag (DiaSorin, Saluggia, Italy). If the pool tested positive, individual samples underwent confirmatory tests, Innotest HIV Antigen mAb (Fujirebio Europe, Gent, Belgium) and HIV BLOT 2·2 (MP Diagnostics, Singapore). Among the 10 044 samples processed, eight were confirmed positive (0·08%, 95% confidence interval 0·03-0·16%), all were males and age was >50 in 3 (37·5%). If projected to the entire population of the Pavia province, this would result in approximately 1000 people unaware of their HIV infection, with age older than expected. In Italy, HIV testing is voluntary, universally free-of-charge and (upon request) anonymous. Nevertheless, this study demonstrates that it is suboptimally employed, and that new strategies and population-level actions will be needed to achieve better implementation of HIV testing and HIV control in our province.

Ganglioneuroma of parapharyngeal region.

In this article, we describe a case of ganglioneuroma observed in a 27-year-old woman. The tumor was found in an unusual location, the parapharyngeal space. The lesion was asymptomatic and was surgically excised after a fine-needle aspiration biopsy that was considered inadequate. The lesion measured 4 x 3 cm and was capsulated. Two distinct cells groups were identified: ganglion cells and Schwann cells placed in a loose myxoid stroma. Immunohistochemical stains (performed with the following monoclonal antibodies: high-molecular-weight cytokeratins, vimentin, neuron-specific enolase, neurofilaments, and S100) confirmed the diagnosis of ganglioneuroma. The pathologic findings and a review of recent literature are discussed.

Biophenotypes and survival of BRCA1 and TP53 deleted breast cancer in young women.

The aim of this study was to examine the loss of heterozygosity (LOH) of BRCA1 (17q21) and TP53 (17p13.1) in early-onset breast cancer patients; to correlate biopathological characteristics with molecular alterations; and to investigate the survival of LOH-related cancers. BRCA1 and TP53 LOH were evaluated in 78 early-onset breast cancers (< or = 40 years, Group 1) and 80 patients with age > 55 years (Group 2). Cases were characterized for multiple biological markers (ER, PR, proliferation index (PI), NEU and p53). LOH was carried out on microdissected paraffin embedded tissues; microsatellites D17S855 (BRCA1) and D17S786 (TP53) were amplified by fluorescent PCR and analyzed by an automated DNA sequencer. Early-onset breast cancers showed a higher frequency of ductal histotype (89.7% vs. 56.3% p < 0.001), node-positive (53.8% vs. 38.7%), larger size (p = 0.017), higher mitotic rate (p = 0.025), higher nuclear and final grade (p = 0.01 and p = 0.001, respectively). D17S855 LOH was 32.8% in group 1 vs. 21% in group 2; D17S786 LOH was 50.7% vs. 31.3% (p = 0.03), respectively. BRCA1 LOH was correlated with higher PI (p = 0.032) and higher p53 expression (p < 0.001) in group 1 and with higher NEU expression (p = 0.028) in group 2. TP53 LOH was correlated with p53 overexpression (p = 0.03) in group 1. A worse clinical outcome in early-onset LOH related cancers emerged from follow-up data: TP53 and BRCA1 LOH were associated with a shorter relapse free interval (RFI) (p = 0.03) and a poorer overall survival (OS) (p = 0.04), respectively. This study underlines different biological profiles in the two age groups investigated, probably reflecting different mechanisms of carcinogenesis. In accordance with adverse histopathological features in early-onset patients, LOH-related cancers have an unfavorable prognosis.

[Aneurysmatic fibrous histiocytoma: case report and reivew of the literature]. / Istiocitoma fibroso aneurismatico: descrizione di un caso e revisione della letteratura.

A case of aneurysmal fibrous histiocytoma is described. The patient is a 26-year-old man with a reddish nodule on the back, recently presenting a volume increase. The tumor was composed of fascicles of short spindle cells, histiocyte-like and inflammatory cells, and blood-filled spaces, mimicking vascular channels but lacking an endothelial lining. Immunohistochemical analysis (performed with the following monoclonal antibodies: smooth muscle actin, vimentin, desmin, CD-31, CD-34, CD-68) showed only vimentin positively on neoplastic cells. We discuss the differential diagnostic hypotheses and review the literature on this subject.

Quantitative immunoprofiles of breast cancer performed by image analysis.

OBJECTIVE: To determine the biopathologic profiles of breast cancer for greater knowledge of tumor natural history and clinical outcome. STUDY DESIGN: In 99 in situ (ISC) and 2718 infiltrating breast carcinomas (IC), biologic markers (estrogen receptor [ER], progesterone receptor [PR] proliferation index, cerbB-2/NEU, p53, bcl-2 and DNA ploidy) were evaluated with an image analysis system (CAS 200/486). In 105 mixed invasive cancers with size < or = 1 cm, a separate analysis of in situ (ISCm) and invasive component (ICm) was obtained. A clinical study of 836 invasive breast cancers was performed. RESULTS: Different biophenotypes were obtained: among ISCs, cribriform type exhibited biologic behavior similar to that of normal breast tissue (ER+, PR+, proliferation index [PI] low, NEU-, p53-, bcl-2+) the opposite profile was displayed by comedo type, and intermediate phenotypes were observed in noncomedo and lobular types. Comparing ISC and ISCm, PI and p53 expression had the highest levels in ISCm with respect to other groups. NEU overexpression exhibited a decreasing value from ICm to IC. Younger women (< or = 40 years) with IC demonstrated a worse biologic profile (high PI, p53+, ER- and size > 2 cm). In multivariate analysis, PI and NEU in node-negative patients, and NEU, PR and size in node-positive ones emerged as prognostic parameters. CONCLUSION: The results underline the importance of the quantitative biologic profile for defining tumor behavior and patient management.

Modulation of biomarkers in minimal breast carcinoma: a model for human breast carcinoma progression.

BACKGROUND: The widespread use of diagnostic breast imaging has yielded an increase in the detection of in situ, microinvasive, and small invasive carcinomas and has provided opportunities to study the earliest stages of breast carcinoma development. The authors of this report analyzed the pathobiologic features of 577 minimal breast carcinomas (MBCs), including in situ carcinomas and invasive carcinomas < or =1 cm, according to the definition given by Hartmann in Cancer (1984;53:681-4). METHODS: Estrogen and progesterone receptors (ER and PR), proliferation index (PI), and p53 and neu expression were studied by immunohistochemical technique and measured by quantitative image analysis in 99 pure in situ carcinomas (ISCp); in 105 mixed invasive/in situ carcinomas, with a separate analysis of in situ (ISCm) and invasive (ICm) components; and in 373 invasive carcinomas < or =1 cm (IC). Follow-up data were available for 164 invasive carcinomas. RESULTS: A progressive increase in the levels of hormone steroid receptors, from the lowest in ISCm to the highest in IC, was observed (ER, P< 0.001; PR, P=0.005). Levels of PI and p53 expression were higher in ISCm than in the other categories (PI, P=0.007; p53, P=0.046). Overexpression of neu was greater in ICm than in IC (P=0.013). Younger women (< or =40 years) with invasive carcinoma had worse biologic profiles, with lower ER (P < 0.001) and higher PI (P=0.021), neu (P=0.008), and p53 (P=0.040). It was demonstrated clinically that PI and neu were the biologic markers with the highest predictive prognostic values in univariate analysis (PI for recurrence, P < 0.015; neu for recurrence and overall survival, P < 0.001 and P < 0.007, respectively) and in multivariate analysis (neu for recurrence and overall survival, P < 0.007 and P < 0.017, respectively). CONCLUSIONS: Biologic phenotypes of MBC can be interpreted as reflecting a dimension of neoplastic progression capacity that is independent of tumor size. This study suggests that biologic markers can be integrated with traditional pathologic indicators for accurate staging of patients.

Biological profile of in situ breast cancer investigated by immunohistochemical technique.

In 74 in situ breast cancers an immunohistochemical study for estrogen (ER) and progesterone (PR) receptors, proliferation index (PI), and c-erbB-2, p53, and bcl-2 overexpression was performed. Cases were categorized as ductal carcinoma in situ (DCIS) comedo: 24.3% of cases; DCIS non comedo: 27% of cases; DCIS cribriform: 5.4% of cases; lobular carcinoma in situ (LCIS): 16.3% of cases; mixed carcinoma in situ: 27% of cases. Quantitation of immunohistochemical results was obtained with an image analysis computerized system (CAS 200). The cutoff values used were: 10% of positive area for ER, PR, NEU, and bcl-2; 5% of positive area for p53; 13% of PI for proliferative activity. DCIS cribriform and LCIS displayed a higher positivity for ER (92.6 and 93.8% of cases); DCIS cribriform and DCIS non comedo a higher for PR (89 and 75.3%); DCIS comedo presented the highest values for PI (65.4%), NEU (72.8%), and p53 expression (37.3%). All DCIS cribriform and DCIS non comedo and 99.6% of LCIS expressed bcl-2. The results underscore the importance of biological characterization of breast carcinoma in situ with the aim to define lesions natural history.

MIB-1 proliferative activity in invasive breast cancer measured by image analysis.

AIMS: To determine cell proliferation in infiltrating breast carcinomas. METHODS: Using the MIB-1 monoclonal antibody, the proliferation index was measured in paraffin wax sections of 871 breast cancers. The MIB-1 proliferation index was compared with other markers of disease progression: size, lymph node status, histotype, oestrogen and progesterone receptor status, expression of p53 and Neu, and DNA ploidy. All parameters were measured using image analysis. In 347 tumours, the MIB-1 and Ki-67 proliferation indexes were compared. Follow up data were available for 170 cases (median 66.5 months). RESULTS: Of the tumours, 314 (36%) had a high proliferation index. The MIB-1 proliferation index was correlated directly with size, nodal status, overexpression of p53 and Neu, and the DNA index; and inversely with oestrogen and progesterone receptor status. The correlation between MIB-1 and Ki-67 proliferation indexes was statistically significant. In patients with pT1 tumours, a low proliferation index correlated with a longer relapse-free interval and overall survival; node negative patients with a low proliferation index had a longer overall survival. CONCLUSIONS: The MIB-1 proliferation index is a reliable, practical and useful method of measuring proliferative activity and is an important predictor of clinical behaviour.

Biophenotypes of breast carcinoma in situ defined by image analysis of biological parameters.

In 50 in situ breast cancers an immunohistochemical study, evaluating estrogen (ER) and progesterone (PR) receptors, Proliferation Index (PI), c-erbB-2/Neu and p53 expression was performed. According to histopathological diagnosis, cases were classified as follows: 14 comedo, 8 solid, 5 micropapillary, 6 lobular, 3 papillary, 1 apocrine and 12 mixed in situ carcinomas. The quantitation of immunohistochemical results was obtained with an image analysis computerized system (CAS 200) with a lesion-field method; tumors were subdivided in fields (1177) histologically homogeneous, with 40 x microscopic objective. For ER, PR, Neu and p53, 10% of the positive area was used as cut-off value; 13% was used for PI. Cribriform and lobular types showed a higher positivity for ER (92.1% and 95.5% of the fields); cribriform and papillary a higher for PR (92.6% and 93.9%). Comedo variant demonstrated the higher PI (52.7%), Neu and p53 expression (67.7% and 43%). A cluster analysis performed on 608 fields, defined two groups according to biological homogeneous criteria. The results obtained identify the different biophenotypes of in situ carcinomas, suggesting the possibility of multiple cancerogenetic ways with a different weight of biological events.

Application of quantitative analysis to biologic profile evaluation in breast cancer.

BACKGROUND: The biologic profile of 907 infiltrating breast carcinomas was determined considering estrogen receptor (ER) and progesterone receptor (PR), proliferation index (PI) and c-erbB-2/Neu expression. The relationship with pathologic parameters (lymph node status, size, histotype) were studied by a multivariate analysis. The clinical prognostic power of biologic profile also was evaluated for 265 patients. METHODS: In 907 infiltrating breast carcinomas, the quantitation of ER, PR, an PI was obtained with an image analysis system (CAS 200, Becton Dickinson Cell Analysis Systems, San Jose, CA); Neu was evaluated semiquantitatively. A clinical study of 265 patients was performed (median follow-up, 42.5 months). RESULTS: Seventy-seven percent of tumors were ER-positive, 70% were PR-positive, 58% had a high PI, and 35% were Neu-positive. The overall analysis indicated a direct correlation between ER and PR (Spearmans' rho [rs] = 0.47, P < 0.001) and an inverse correlation between PI and ER (rs = -0.39, P < 0.001), PI and PR (rs = -0.32, P < 0.001), Neu and ER (rs = -0.20, P < 0.001), and Neu and PR (rs = -0.21, P < 0.001). Cluster analysis, performed based on the biologic profile (ER, PR, PI, c-erbB-2/Neu expression), identified two final groups of tumors with different pathologic features. This study showed a longer relapse free interval for patients with ER- and PR- positive tumors (P = 0.016 and P = 0.007) and low PI and Neu-negative tumors (P < 0.001 and P = 0.047). CONCLUSIONS: These results stress the importance of the biologic profile for defining tumor behavior and patient management, leading to integration of, and eventually the substitution for, the actual staging system.

Cancer incidence and mortality in the province of Ferrara 1989-1990.

BACKGROUND: Mortality data have clearly highlighted the province of Ferrara as an area with a particular distribution of tumors strictly related with environmental factors. METHODS: The project of a tumor registry has been planned for a better description of cancer incidence and for a deeper insight into etiologic factors, considering the typical features of the province from geographic and occupational points of view. RESULTS: This study presents the registration results of the first 2 years, in order to verify the quality level of data recruitment and to confirm that observed in previous studies. The population covered by the registry was 151,968 males and 165,835 females, with high representation of the elderly. In this period 2,087 tumors in men and 1,778 in women were observed. Lung cancer reaches one of the highest levels in Italy, according to that observed in Lombardy and Veneto regions and the northern Adriatic coast. Incidence and mortality are, however, significantly higher than in other Emilia-Romagna areas, as pointed out by the registries of Parma, Modena and Forii. Colon cancer also presents high frequencies in comparison with neighboring areas, whereas non-Hodgkin lymphomas reach the highest level in Italy. Gastric tumors, although well represented in males and females, show lower levels than the high-risk neighboring Romagna region. In women, a low incidence of cervix uteri-tumors and high levels of breast cancer have also been observed. CONCLUSIONS: The distribution of such neoplasms and the differences observed among neighboring areas deserve further analytical studies, with the aim of a better reading of cancer onset and diffusion. The quality of data obtained (about 70% of histocytologic confirmations, and 5% of "final" death-certificate-only cases), appears to reach satisfying levels, considering the starting phase of the registry.

Uremic polyneuropathy: a clinical and electrophysiological study in 135 short- and long-term hemodialyzed patients.

Twenty neurophysiological parameters were employed to evaluate the presence and the degree of peripheral neuropathy (PNP) in a cohort of 135 patients (pts) on regular dialysis treatment (RDT) for 2 to 184 months. The 135 pts were divided into 3 groups according to the duration of RDT (group I: 52 pts with less than 5 yrs; group II: 46 pts 5 to 10 yrs; group III: 37 pts 10 to 15 yrs). Each group was then divided into two subgroups according to age (less or more than 47 yrs) to evaluate the influence of age on PNP. Correlations of electrophysiological parameters with some biochemical parameters (urea, creatinine, PTH) were looked for. The presence of clinical PNP was evaluated according to the Bolton classification: in group I, 50% of pts have mild PNP; in group II, 45.7% of pts have mild PNP; in group III, 81.1% have mild, 10.8% have moderate and 2.7% of pts have severe PNP. In as many as 84.4% of the 135 pts at least one of the 20 parameters studied had abnormal values and in 63% two or more parameters were abnormal. Of 20 parameters evaluated separately in the 3 groups only three showed abnormal mean values: sural nerve latency in all 3 groups; sural nerve Sensory Conduction Velocity (SCV) and peroneal nerve Max. Motor Conduction Velocity (MCV) in group III. Five parameters referring to ulnar nerves and two referring to the sural nerve were significantly more impaired in the group of pts with the longest duration of RDT and in this group the impairment was more severe in older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Long-term clinical results with monocomponent insulin (MC lente) in infantile and juvenile diabetes]. / Risultati clinici a lungo termine nel diabete infanto-giovanile trattato con insulina monocomponente (lenta MC)

The clinical role of insulin-antibody formation, with reference to the monocomponent insulin treatment (MC), is discussed in a series of diabetological conditions. On the basis of a five-year-experience, personal results with a MC Lente treatment are presented in 32 cases of juvenile diabetes subdivided as follows: 3 cases with insulin allergy, 5 cases with insulin lipoatrophy, 13 cases with high insulin requirement, 4 cases with brittle diabetes, 7 cases with diabetic microangiopathy (retinal and, or renal). The circulating antibody level was estimated by IgG-Insulin-Binding Capacity (IB), according to Christiansen. After transfer from conventional to MC insulin treatment it was observed: -- disappearance of allergy and total remission of lipoatrophy, in parallel with a reduction of IB titer; -- decrease in insulin requirement and stabilisation of labile diabetic control, not always in concomitance with IB reduction; -- deterioration of advanced diabetic retinopathy and, or nephropathy in spite of IB reduction. It is concluded that MC insulin constitutes a major tool in the treatment of the above mentioned diabetic conditions, except for advanced microangiopathy. Thus a MC insulin treatment should be started, as a rule, in newly diagnosed diabetics, to possibly prevent such complications. However further development of insulin purification techniques, with removal of residual pro-insulin antigenic sites, is to be considered.