PROGNOSTIC SIGNIFICANCE OF THE CO-EXPRESSION OF p53 AND c-erbB-2 PROTEINS IN BREAST CANCER

The immunohistochemical expression of p53 and c-erbB-2 gene proteins was examined in a series of 130 breast adenocarcinomas. This study intended to investigate whether the frequency of the altered expression of the tumour suppressor gene p53 and the overexpression of the oncogene c-erbB-2 in breast cancer tissue cells correlated with other variables known to affect the biological behaviour of these tumours and the overall survival of the patients (median follow-up time: 6 years). The expression of p53 protein and c-erbB-2 gene product was evaluated immunohistochemically. Expression of p53 protein was detected in 30 (23 per cent) of the neoplasms examined, while 26 (20 per cent) out of the 130 cases demonstrated positive c-erbB-2 immunoreactivity. There was a statistically significant association between p53 protein expression and primary tumour size, lymph node involvement, and oestrogen receptor positivity. The incidence of c-erbB-2 positivity was significantly correlated with high tumour grade, axillary node invasion, large tumour size, and the absence of steroid receptors. p53 immuno-expression was clearly associated with c-erbB-2 protein overexpression. Concomitant p53 and c-erbB-2 positive immunolabelling, which emerged in 14 out of the 130 cases (10·7 per cent), was clearly associated with high grade, large size, positive nodal status, ductal infiltrating (NOS) histological type, and low values of progesterone receptors. Overall survival of patients was not significantly related to the immunoreactivity of either p53 or c-erbB-2 considered separately, whereas there was a clearly significant trend to worse overall prognosis in cancers with double p53/c-erbB-2 positive phenotype. The simultaneous immunodetection of p53/c-erbB-2 appears to have greater negative prognostic relevance than their separate expression.     

Circadian Modulation of Ventricular Tachycardia Cycle Length Variability in ICD Patients with Dilated Cardiomyopathy

VT is usually characterized by stability of the RR intervals after a few cycles from the onset. The aim of this study was to evaluate the VT cycle length (VTCL) variability in patients with dilated cardiomyopathy (DCM), in whom a third-generation ICD was previously implanted. Eighty-three episodes of VT were analyzed in 10 patients (8 male, 2 female, 65 ± 6 years) with DCM, and NYHA Class II (7 patients) or III (3 patients). As an index of VTCL variability, the coefficient of variance of the last 15 consecutive RR intervals (CVRR) of the detected and stored VT by the device was considered. The mean value of the RR intervals and the mean value of CVRR of the VT episodes recorded during day versus night time were compared. Fifty-five VT episodes were recorded during the day and 28 episodes during the night time. The mean RR intervals of VT episodes during day time was 335 ± 29 ms and during the night time was 350 ± 22 ms (P = NS). The mean CVRR of VT episodes during day time and night time were 2.83 ± 0.52 and 3.36 ± 0.48, respectively (P = 0.017). In conclusion, a circadian modulation of VTCL variability exists in patients with DCM. The VTCL variability is less during day time compared to night time. A possible explanation is a circadian alteration of sympathovagal balance modifying the electrophysiological properties of the arrhythmogenic substrate.     

Immunohistochemical evaluation of nm23-H1 gene product in transitional cell carcinoma of the bladder

The expression of the nm23-H₁ gene has been suggested to have an inverse association with metastases in certain tumours. The aim of this study was to investigate the relationship of nm23-H₁ immunohistochemical expression with pathological tumour variables and survival in a series of transitional cell carcinomas (TCCs) of the bladder. Formalin-fixed, paraffin-embedded archival tissue from 87 carcinomas (T_a-T₁ 45 cases) and T₂-T₄ (42 cases) was immunostained (Strept ABC/ HRP) with the NDPK-A monoclonal antibody (NDPK-A) against nm23-H₁ protein. The tumours had already been evaluated for immuno-expression of p53 protein. In addition, DNA analysis was performed by flow cytometry. Results were analysed using the linear trend in proportions test, the Fisher's exact test and multivariate analysis. Paradoxically, advanced tumour stage showed significant correlation with nm23-H₁ immunopositivity in muscle invasive TCCs (P_t = 0.01). Patients with nm23-H₁ positive, muscle invasive TCCs had a worse prognosis at a level of suggestive statistical significance (P_F = 0.08). In multivariate analysis, using a Cox's proportional hazards survival model with six variables, tumour grade, disease stage and synchronous p53 and nm23-H₁ detection showed significant correlation with poor patient survival ( P  = 0.014, P  = 0.049 and P  = 0.05, respectively).     

Metastatic low-grade endometrial stromal sarcoma of clitoris: report of a case

Low-grade endometrial stromal sarcoma (ESS) is an uncommon neoplasm, which has a highly recurrent nature. A review of the literature revealed that only one case of low-grade ESS, arising within the vulva from a focus of endometriosis, has been previously published. We describe an additional case of low-grade ESS arising within the vulva and to the best of our knowledge the first report of low-grade ESS metastasized to clitoris. A 46-year-old woman was admitted to our hospital due to a heavy uterine bleeding. A physical examination revealed a lesion in clitoris, which exhibited a densely cellular mesenchymal neoplasm on microscopy. On the basis of the pathologic features alone, a differential diagnosis of a low-grade ESS and cellular leiomyoma was considered. Seven months later, the patient presented again with excessive uterine bleeding and a total hysterectomy was performed. A tumor of white-tan, whorled appearance was found. Its features were suggestive of low-grade ESS. Taking into account the possible extrauterine location of an ESS and reviewing the first case, a diagnosis of rare low-grade ESS metastasized to clitoris was made.     

Atrial Septal Pacing to Synchronize Atrial Depolarization in Patients with Delayed Interatrial Conduction

The current method of pacing the right atrium from the appendage or free wall is often the source of delayed intraatrial conduction and discoordinate left and right atrial mechanical function. Simultaneous activation of both atria with pacing techniques involving multisite and multilead systems is associated with suppression of supraventricular tachyarrhythmias and improved hemodynamics. In the present study we tested the hypothesis that pacing from a single site of the atrial septum can synchronize atrial depolarization. Five males and two females (mean age 58 ± 6 years) with drug refractory paroxysmal atrial fibrillation (AF) were studied who were candidates for AV junctional ablation. All patients had broad P waves (118 ± 10 ms) on the surface ECG. Multipolar catheters were inserted and the electrograms from the high right atrium (HRA) and proximal, middle, and distal coronary sinus (CS) were recorded. The atrial septum was paced from multiple sites. The site of atrial septum where the timing between HRA and distal CS (d-CS) was ≤ 10 ms was considered the most suitable for simultaneous atrial activation. An active fixation atrial lead was positioned at this site and a standard lead was placed in the ventricle. The interatrial conduction time during sinus rhythm and AAT pacing and the conduction time from the pacing site to the HRA and d-CS during septal pacing were measured. Atrial septal pacing was successful in all patients at sites superior to the CS os near the fossa ovalis. During septal pacing the P waves were inverted in the inferior leads with shortened duration from 118 ± 10 ms to 93 ± 7 ms (P < 0.001), and the conduction time from the pacing site to the HRA and d-CS was 54.3 ± 6.8 ms and 52.8 ± 2.5 ms, respectively. The interatrial conduction time during AAT pacing was shortened in comparison to sinus rhythm (115 ± 18.9 ms vs 97.8 ± 10.3 ms, P < 0.05). In conclusion, simultaneous activation of both atria in patients with prolonged interatrial conduction time can be accomplished by pacing a single site in the atrial septum using a standard active fixation lead placed under electrophysiological study guidance. Such a pacing system allows proper left AV timing and may prove efficacious in preventing various supraventricular tachyarrhythmias.