Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma.

BACKGROUND: The down regulation of protein p27(kip1) (p27) in most cases of thyroid cancer has relevant diagnostic and prognostic implications. However, the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma expresses more p27 than benign oxyphilic lesions do. AIM: To evaluate the mechanism underlying this difference in expression of p27. METHODS: Because high levels of cyclin D3 lead to p27 accumulation in cell lines and clinical samples of thyroid cancer, the immunocytochemical pattern of cyclin D3 in oxyphilic (n = 47) and non-oxyphilic (n = 70) thyroid neoplasms was investigated. RESULTS: In the whole study sample, there was a significant correlation between p27 and cyclin D3 expression (Spearman's r: 0.64; p<0.001). The expression of cyclin D3 and p27 was significantly higher in the oxyphilic variant of follicular carcinomas than in non-oxyphilic carcinomas (p<0.001). In the former, cyclin D3 overexpression and p27 accumulation were observed in a median of 75% and 55% of cells, respectively. In co-immunoprecipitation experiments, the level of p27-bound cyclin D3 was much higher in oxyphilic neoplasias than in normal thyroids and other thyroid tumours. CONCLUSION: These results show that increased p27 expression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma results from cyclin D3 overexpression.

Radiofrequency (pacing and thermic effects) in the treatment of sleep-disordered breathing.

Radiofrequency, whether it is used for pacing or for its thermal liberation properties, has been investigated as a treatment for sleep-disordered breathing. Diaphragmatic pacing has a long history. The problems associated with pacing, which are related to patient selection, equipment failure, disturbances at the electrode/nerve interface, neuromuscular function failure, muscle fatigue, and the physiological consequences of stimulation, will have to be resolved with XIIth nerve stimulation. Radiofrequency thermal ablation has been applied on the tongue of an animal model. In man, turbinates, soft palate tissue and the base of tongue have been treated. These feasibility studies have demonstrated that obstructive sleep apnea syndrome and upper airway resistance syndrome can be completely controlled using radiofrequency thermal ablation in some subjects. These results can be obtained without complications related to speech, taste or swallowing. The treatment can be administered as an outpatient procedure, but many applications are needed, and treatment may span 6 months. Too high a level of radiofrequency will cause pain or otherwise avoidable complications. The determination of which patients will benefit most from these procedures will require further multi-center, placebo-controlled studies.

Upper airway resistance syndrome and its treatment.

Although upper airway resistance syndrome (UARS) is being recognized by a growing number of specialists, its prevalence remains unknown. UARS is associated with nocturnal and daytime complaints and oro-naso-maxillo-mandibular signs. Spectrum analysis of the nocturnal sleep EEG from the central leads indicates significant differences in absolute power in the 12-14 Hz and the 7-9 Hz bands of UARS patients compared to controls. The 0.5-2.0 Hz band also appears to be involved when analyses performed on matched controls are compared to results obtained in subjects treated with nasal CPAP. Several treatment avenues--nasal CPAP, dental devices, surgical procedures, and radiofrequency thermal ablation--have been used for the treatment of UARS. The number of subjects treated have been too low and the protocols too limited to arrive at appropriate outcome recommendations, but many of the approaches have shown positive results, suggesting the possibility of several treatment avenues.

Validation of the sleep-EVAL system against clinical assessments of sleep disorders and polysomnographic data.

OBJECTIVES: To validate the Sleep-EVAL expert system, a computerized tool designed for the assessment of sleep disorders, against polysomnographic data and clinical assessments by sleep specialists. DESIGN: Patients were interviewed twice, once by a physician using Sleep-EVAL and again by a sleep specialist. Polysomnographic data were also recorded to ascertain diagnoses. Agreement between diagnoses generated by Sleep-EVAL and those formulated by sleep specialists was determined via the kappa statistic. SETTINGS: Sleep disorder centers at Stanford University (USA) and Regensburg University (Germany). PATIENTS: 105 patients aged 18 years or over. INTERVENTIONS: NA. RESULTS: Sleep-EVAL made an average of 1.32 diagnoses per patient, compared with 0.93 for the sleep specialists. Overall agreement on any sleep-breathing disorder was 96.9% (Kappa .94). More than half of the patients were diagnosed with obstructive sleep apnea syndrome (OSAS); the agreement rate for this specific diagnosis was 96.7% (Kappa .93). CONCLUSIONS: The findings indicate that the Sleep-EVAL system is a valid instrument for the recognition of major sleep disorders, particularly insomnia and OSAS.

The prognostic significance of tumor angiogenesis in nonaggressive and aggressive basal cell carcinoma of the human skin.

Basal cell carcinoma (BCC) is currently the most common cutaneous cancer found in humans. Although it generally shows a relatively benign course (BCC1), some cases of BCCs show "aggressive" behavior, rapidly infiltrating deeper structures, or metastasizing (BCC2). Until now, the traditional histological diagnostic criteria have failed to discriminate unequivocally between BCC1 and BCC2. Therefore, there is still a need to find reliable prognostic indicators that correlate with outcome and may detect patients at high risk for BCC recurrence, or metastasis and death. Recent studies have suggested that there is a significant correlation between tumor angiogenesis, expressed as the microvessel density within and toward a tumor, tumor aggressiveness, and the overall survival of patients with solid tumors. In this study, the authors examined the angiogenic rate in human cutaneous BCCs, to establish if it correlates with their biological behavior. Vessels were highlighted by immunocytochemical staining for FVIII-related antigen in formalin-fixed, paraffin-embedded tissues. All BCC2 samples of this series showed a significantly higher microvessel count than did BCC1. The existence of a significant discrepancy between the neovascularization in BCC1 and BCC2 suggests that the angiogenetic process may be an important step in the acquisition of the aggressive (malignant) phenotype in human. BCCs. The findings of the present study seem to establish a correlation between tumor vascularization and clinicobiological parameters of aggressiveness in BCC. Considering the emerging studies on the possible clinical use of substances interfering with the angiogenetic process, it is possible that the local therapy for BCCs could become less destructive, with consequent improvement in the quality of life of these patients, apart from the prolongation of the overall survival. From this view-point, the assay of microvessel density might be helpful in selecting patients with cutaneous BCCs at high risk for recurrence or metastasis, who could benefit ab initio from additional therapies and closer follow-up.

Cyclin dependent kinase inhibitor p27Kip1 expression in normal and neoplastic cervical epithelium.

AIM: To investigate whether there is loss of the p27Kip1 protein in developing cervical cancer and whether p27Kip1 immunoreactivity has any relation to the proliferative indicator Ki-67. METHODS: The expression of p27Kip1 and Ki-67 was assessed by immunohistochemistry in serial sections from normal epithelium (13), low grade (27) and high grade (19) squamous intraepithelial lesions (LSIL, HSIL), and invasive cervical cancer (23). In the SIL cases the presence of human papillomavirus (HPV) genomic sequences was assessed by in situ hybridisation. The results were evaluated by image analysis, and reported as mean score of the percentage of p27Kip1 and of Ki-67 positive cells in each histological group. RESULTS: In general, p27Kip1 immunostaining was related to squamous differentation, and was intense in normal epithelium (47%), while it was reduced in SIL lesions as an effect of the decreased number of differentiating cells. However, decrease in the p27Kip1 expression was more evident in LSIL (36%) than in HSIL (39%); in the latter, p27Kip1 had a different intraepithelial distribution in that the staining extended to the basal cells. The average levels of p27Kip1 were similar in SIL lesions associated to low, intermediate, and high risk HPV types. Compared with normal epithelium and dysplasia, invasive cancer showed significantly lower p27Kip1 levels (23%). There was no relation between p27Kip1 and Ki-67 labelling indices in any of the histological groups examined. CONCLUSIONS: A reduction in p27Kip1 protein occurs in cervical cancer independently of the proliferative status. The changes in p27Kip1 expression may be related to the unregulated kinetics of developing cervical cancer.

p27 Kip1 protein expression in Hashimoto's thyroiditis.

AIMS: Hashimoto's thyroiditis (HT) is an autoimmune disease in which both proliferation and apoptosis are enhanced. p27(Kip1) protein protects tissues from disease mechanisms that involve excessive cell proliferation and apoptosis. This study investigated whether there is loss of p27(Kip1) expression in HT and whether p27(Kip1) immunoreactivity has any relation to the proliferative indicator Ki-67. Because p27(Kip1) is regulated through either degradation, mediated by the S phase kinase associated protein 2 (Skp2), or sequestration, via D3 cyclin, the expression of these proteins was also investigated. METHODS: Immunohistochemistry was used to assess p27(Kip1), Ki-67, Skp2, and cyclin D3 expression in 19 cases of HT and in 10 normal thyroids. The results were evaluated by image analysis and reported as labelling indices (LIs) in both groups. RESULTS: The p27(Kip1) LI was lower in HT than in normal thyroid (28% v 75%; p < 0.001), whereas Ki-67 (1.13% v 0.13%), Skp2 (0.74% v 0.15%), and cyclin D3 (1.56% v 0.00%) LIs were higher in HT than in normal thyroids (p < 0.001). There was no correlation between p27(Kip1) and the expression of Ki-67, Skp2, and cyclin D3. CONCLUSIONS: p27(Kip1) downregulation is not exclusive to tumours but occurs also in HT, independently of the proliferative status and of changes in Skp2 and cyclin D3 expression. Further investigation is required to understand the mechanisms leading to p27 deregulation because these observations suggest that the regulation of p27(Kip1) expression in epithelial thyroid cells may play a role in HT pathogenesis.

Immunohistochemical expression of mdm2 and p21WAF1 in invasive cervical cancer: correlation with p53 protein and high risk HPV infection.

AIM: To investigate the immunocytochemical staining pattern of mdm2 and p21WAF1 proteins in invasive cervical cancer and to determine its relation with the expression of p53 and with the high risk HPV infection. METHODS: Immunocytochemistry for p53, mdm2, and p21WAF1 was performed in 31 paraffin embedded sections of invasive cervical cancer. The results were assessed by image analysis, evaluating for each protein the optical density of the immunostained area, scored as percentage of the total nuclear area. The presence of high risk human papillomavirus (HPV) infection was detected by using the polymerase chain reaction. RESULTS: Immunostaining for both mdm2 and p21WAF1 was correlated with p53 expression; however, the correlation between p53 and mdm2 (R = 0.49; p < 0.01) was more significant than between p53 and p21WAF1 (R = 0.31; p < 0.05); the less stringent correlation between p53 and p21WAF1 might reflect the p53 independent mechanisms of p21WAF1 induction. Similar average levels of p53, mdm2, and p21WAF1 immunostaining were found in the presence or absence of high risk HPV-DNA, without significant differences between the two groups. CONCLUSIONS: These data suggest that mdm2 and p21WAF1 proteins are expressed in invasive cervical cancer and that their immunocytochemical staining pattern is not abrogated by the presence of high risk HPV genomic sequences.

Variability of respiratory effort in relation to sleep stages in normal controls and upper airway resistance syndrome patients.

OBJECTIVE: Investigation of the role of sleep states on the respiratory effort of controls and subjects with upper airway resistance syndrome (UARS) using nasal cannula/pressure transducer system and esophageal manometry. PATIENTS AND METHODS: One night's monitoring of sleep and breathing, including the determination of peak end inspiratory esophageal pressure (respiratory effort) with esophageal manometry and flow limitation with nasal cannula. Analysis of the data, breath-by-breath, using visual inspection and a computerized program. Setting - a university sleep laboratory. Patients were nine men with UARS and nine control men matched for age, ethnicity, and body mass index. RESULTS: A modulation of respiratory effort by sleep state and stages is seen in all subjects, the lowest noted during REM sleep and the highest associated with Slow Wave Sleep. When total nocturnal breaths are investigated, a significant difference between peak end inspiratory esophageal pressure [(Pes)-considered as an index of respiratory effort] is noted between normal subjects and UARS. Two specific breathing patterns, seen primarily in UARS patients, are NREM sleep stage dependent. Crescendos (defined as more negative peak end inspiratory Pes with each successive abnormal breath) occur mostly during stages 1-2 NREM sleep, while segments consisting of regular and continuous, breath-after-breath, high respiratory efforts are associated with Slow Wave Sleep. Depending on sleep stage, visually scored arousal response displays differences in Pes negativity. The termination of the abnormal breathing pattern, always well defined with Pes, is not necessarily associated with a pattern of 'flow limitation' at the nasal cannula tracing, even when a visually scored EEG arousal is present. CONCLUSIONS: UARS patients have significantly more breaths, with more negative peak end inspiratory Pes, than do control subjects. The modulation of peak end inspiratory Pes (an index of respiratory effort) by sleep stage and state differs in UARS patients and control subjects. The nasal cannula/pressure transducer system may not detect all abnormal breathing pattern during sleep. As indicated by the visual sleep scoring, repetitive arousals may lead to more or less severe sleep fragmentation.

Sleep and wakefulness in somnambulism: a spectral analysis study.

OBJECTIVE: The sleep structure and the dynamics of EEG slow-wave activity (SWA) were investigated in 12 young adults and age- and gender-matched controls. METHODS: Polysomnography was performed in subjects with well-documented chronic sleepwalking and in matched controls. Blinded visual scoring was performed using the international criteria from the Rechtschaffen and Kales atlas [A manual of standardized technology, techniques and scoring systems for sleep stages of human subjects. Los Angeles: UCLA Brain Information Service, Brain Research Institute, 1968.] and by determining the presence of microarousals as defined in the American Sleep Disorders Association (ASDA) atlas [Sleep 15 (1992) 173.]. An evaluation of SWA overnight was performed on total nocturnal sleep to determine if a difference existed between groups of subjects, since sleepwalking usually originates with slow-wave sleep. Investigation of the delta power in successive nonoverlapping 4-second windows in the 32 seconds just prior to EMG activity associated with a confusional arousal was also conducted. One central EEG lead was used for all analyses. RESULTS: Somnambulistic individuals experienced more disturbed sleep than controls during the first NREM-REM sleep cycle. They had a higher number of ASDA arousals and presented lower peak of SWA during the first cycle that led to a lower SWA decline overnight. When the investigation focused on the short segment immediately preceding a confusional arousal, they presented an important increase in the relative power of low delta (0.75-2 Hz) just prior to the confusional arousal. CONCLUSION: Sleepwalkers undergo disturbed nocturnal sleep at the beginning of the night. The increased power of low delta just prior to the confusional arousal experienced may not be related to Stages 3-4 NREM sleep. We hypothesize that it may be translated as a cortical reaction to brain activation.

A morphometric approach to the grading of chondroid tumours on fine-needle smears.

A morphometric study was performed on 600 nuclei from 6 benign chondroid tumours (BCL) (3 enchondromas and 3 exostoses), 600 nuclei from 6 well-differentiated chondrosarcomas (WDC) and 200 nuclei from moderately-differentiated chondrosarcomas (MDC) obtained by fine needle aspiration biopsy. The parameters considered were nuclear area, perimeter and maximum diameter. Moving across the three groups of lesions the nuclei appeared progressively larger. A statistical analysis was performed on the three groups. Significant differences between the means of all the parameters considered were observed. The authors suggest that morphometric analysis may be a possible step in the cytologic diagnosis and grading of chondroid tumours.

Primary laryngeal malignant fibrous histiocytoma: a case report.

Malignant fibrous histiocytoma (MFH) of the upper respiratory tract is rare. We report a case of laryngeal MFH in a 78-year-old man. The patient died 8 months after the first surgical treatment. The clinicopathologic features are described, and the importance of electron microscopy and immunohistochemical techniques in the differential diagnosis with so-called "sarcomatoid carcinoma" is stressed. The tumor has an aggressive biological behavior and tends to recur and metastasize.

Follicular variant of papillary carcinoma: cytologic findings on FNAB samples-experience with 16 cases.

Between January 1, 1992 and December 31, 1997, a cytopathological diagnosis of follicular variant of papillary thyroid carcinoma (FVPC) was made on a series of 16 out of 18 patients with palpable nodules who underwent fine-needle aspiration biopsy (FNAB) in our Department. The results of aspiration biopsy were followed by histopathological examination of the surgically excised tissues. There were three false-negative aspirations (16.6%), of which two were probably bound to fine-needle sampling and one due to a mixture of benign and malignant cells which had originally gone unrecognized. The accuracy of the cytopathologic diagnosis in this variant was 88.8%. An analysis of the diagnostic cytopathological criteria was performed, which demonstrated the importance of both architectural features (monolayered and branching sheets, microacinar structures, and their combinations) and nuclear features (presence of nuclear grooves). Background -bound features were mainly represented by dense, nonfilamentous colloid. The cytopathologic findings in FVPC were compared to those found in a series of 10 usual papillary carcinomas (UPC) and 10 follicular neoplasms (FN). These latter had originally been diagnosed by FNAB and were subsequently classified histologically as follicular adenoma (n = 6), follicular carcinoma (n = 3), or adenomatoid colloid nodule (n = 1). Statistical evaluation was performed on the cytopathological findings in the three classes of lesions (FVPC, UPC, and FN) as to their presence and relative frequency or absence by using a nonparametric one-way ANOVA (Kruskall-Wallis) and, where necessary, a Mann-Whitney U test. Papillary cellular fragments and multinucleated giant cells (P < 0.005), nonfilamentous dense colloid, squamoid cells, and syncytia were significantly more represented in UPC than in FVPC (P < 0.05), while histiocytes were significantly more frequent in FVPC (P < 0.005). Other nuclear and/or background features were significant only in the distinction between papillary carcinomas as a group and FN. The cytological differential diagnosis of the FVPC is briefly discussed with relevance to the possible pitfalls caused by its peculiar cyto- and histomorphology.

Epithelioid sarcoma: report of two cases diagnosed by fine-needle aspiration biopsy with immunocytochemical correlation.

Epithelioid sarcoma (ES) is an aggressive soft-tissue malignant tumor generally arising in the distal extremities of young adults. The microscopic diagnosis of ES is often difficult because of its rarity and its possible confusion with other malignant tumors or even with benign granulomatous processes. Two cases of ES and a recurrence of one of these tumors, diagnosed by fine-needle aspiration biopsy (FNAB), are reported. Cytologic smears were quite similar in both cases including the relapse, showing single or loosely arranged groups of medium to large atypical cells. Single cells had well-defined eosinophilic cytoplasms and one or more atypical, eccentrically located nuclei, resulting in a plasmacytoid appearance. Nuclei had fine granular chromatin and one or two large nucleoli. The cells sometimes palisaded along the edges of necrotic material. The immunocytochemical stains showed diffuse cytoplasmic positivity for cytokeratins (CAM 5.2) and both cytoplasmic and cell membrane positivity for vimentin, while S-100 protein and HMB 45 immunostaining were negative, thus supporting the cytological diagnosis of ES, which was subsequently proven on the surgical samples. Diagn. Cytopathol. 1999;21:405-408.

Hodgkin's disease mimicking suppurative lymphadenitis: a possible pitfall in fine-needle aspiration biopsy cytology.

We report one case of nodular sclerosing Hodgkin's disease with uncommon pseudosuppurative presentations in fine-needle aspiration biopsy (FNAB) samples and on histopathologic material. The criteria for cytologic diagnosis include atypical mononuclear cells and diagnostic SR cells in the purulent exudate. This lesion is considered a possible pitfall in FNAB cytology of Hodgkin's disease.

Calcifying epithelial odontogenic tumor (Pindborg's tumor) on fine-needle aspiration biopsy smears: a case report.

A 44-yr-old woman with a long-standing history of painful mandibular swelling was hospitalized for the diagnostic evaluation of an osteolytic mandibular lesion in the premolar-canine area. Fine-needle aspiration biopsy (FNAB) was performed and cytologic smears were characterized by clusters, sheets, and rare isolated pleomorphic cells of the squamoid type, blocks of amorphous material encircled by fibroblasts, and occasional calcifications. A cytological diagnosis of Pindborg's tumor was made, which was confirmed by histopathological examination. Evaluation of DNA ploidy by semiautomated image cytometry produced an aneuploid histogram. The patient is free of residual neoplasm at a 12-mo post-operative interval. The cytological differential diagnosis of this rare odontogenic neoplasm is discussed briefly.

Intraoperative cytology in breast cancer diagnosis: comparison between cytologic and frozen section techniques.

The diagnostic accuracy of frozen section (FS) examination and intraoperative cytology (IOC) has been compared in two different series of breast biopsies in which only one of the two methods has been used. The intraoperative results have been compared with the final histological diagnoses. Five-hundred-ten cases have been investigated by using FS only, and 407 by means of IOC. The two series were comparable because they included the same pathologies; moreover we have subdivided each series into four groups of pathologies to better evaluate the diagnostic accuracy of two methods. The total diagnostic accuracy of FS has been 93.13% vs. 95.33% of IOC. The value of diagnostic accuracy of FS and IOC in the four sub-groups substantially overlapped; there was only a little difference in the group of "various lesions" in which the diagnostic accuracy of IOC was higher. No false positive has been observed in IOC. FS have produced one false positive (0.19%), whereas false negatives have amounted to 1.77% for IOC and to 1.72% for FS. Deferred diagnoses have been 2.95% in IOC and 4.90% in FS examination. For both methods according to Galen and Gambino the following values have been calculated: sensitivity, specificity, efficiency, and predictive value. By comparing the data, the value of the cytological examination in the intraoperative diagnoses results is evident mainly when the latter is coupled with the gross observation.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteomyelitis by Paracoccidioides brasiliensis (South American blastomycosis): cytologic diagnosis on fine-needle aspiration biopsy smears: a case report.

A case of osteomyelitis caused by Paracoccidioides brasiliensis primarily diagnosed by means of fine-needle aspiration biopsy is reported here in a 60-yr-old Italian patient who had lived in Venezuela for 40 yr. The cytologic and electron microscopic features of the exudate aspirated from a left femoral osteolytic area are described, and the differential diagnosis of this mycotic infection is discussed briefly.

Cyclin-dependent kinase inhibitor p27(Kip1) expression in thyroid cells obtained by fine-needle aspiration biopsy: a preliminary report.

Recent studies on paraffin-embedded tissue have shown that the cyclin-dependent kinase inhibitor p27(Kip1) is expressed in normal thyroid cells, whereas it is downregulated in neoplastic cells. This prospective study was undertaken to assess whether p27(Kip1) staining may also be applied to fine-needle aspiration biopsy (FNAB) samples of the thyroid. We present here our preliminary results on 100 FNABs examined for p27(Kip1) expression. p27(Kip1) expression was assessed by immunocytochemistry; the technique was optimized on smears prepared from a normal thyreocyte cell line (TL5), which conspicuously expresses p27(Kip1), and then applied to FNAB samples prospectively collected from 80 cases of nodular goiter and 20 cases of thyroid neoplasms (10 papillary carcinomas and 10 follicular neoplasms). The TL5 cell culture smears showed that methanol fixation, followed by heat-induced antigen retrieval, is the most suitable technique for p27(Kip1) staining on cytological samples. The FNAB smears similarly treated showed high p27(Kip1) expression (75%) in goiter and a significantly lower expression (35%) in neoplasms (P < 0.0001). Our preliminary results show that: 1) p27(Kip1) protein expression can be reliably assessed on cytological samples; and 2) p27(Kip1) stains nonneoplastic and neoplastic samples in a different fashion, and thus is a useful tool in thyroid cytology.

c-erbB-2 expression in FNAB smears and matched surgical specimens of breast cancer.

Most of the data regarding the significance of c-erbB-2 oncogene expression as a prognostic marker in breast cancer have been generated in many large retrospective studies by retrieving the corresponding oncoprotein in archival paraffin embedded sections. Recently, employing fresh breast cancer cells obtained by means of fine-needle aspiration biopsy, we found a rate of c-erbB-2 positive breast tumors (58%) higher than that reported in paraffin-embedded tissue sections by others studies. The present analysis was undertaken to investigate the impact of routine tissue processing on the preservation of the c-erbB-2 immunoreactivity. This issue was addressed by assessing the relative rate of c-erbB-2 oncoprotein immunodetection on FNAB smears and matched surgical specimens of breast cancer. The expression of c-erbB-2 oncoprotein was evaluated using the alkaline phosphate-anti-alkaline phosphatase (APAAP) technique in 54 breast aspirates and corresponding surgical specimens of primary breast cancer. Twenty-six (48%) smears and 23 (43%) matched paraffin sections gave specific signal for c-erbB-2 oncoprotein. The slightly higher incidence of c-erbB-2 expression found on smears seems to be mainly due to the better antigen preservation in the fresh cytological preparations. We conclude that routine histological processing may affect c-erbB-2 immunoreactivity; therefore, in mounting prospective studies, it is advisable to assess c-erbB-2 status in fresh tissue. Moreover, the assessment of c-erbB-2 expression on aspirate samples may yield additional information to the pre-surgical prognostic evaluation of breast cancer diagnosed by FNAB.