Cabozantinib Plus Durvalumab in Patients With Advanced Urothelial Carcinoma After Platinum Chemotherapy: Safety and Preliminary Activity of the Open-Label, Single-Arm, Phase 2 ARCADIA Trial.

BACKGROUND: Durvalumab and cabozantinib have shown single-agent activity in patients with metastatic urothelial carcinoma (UC). ARCADIA is a phase 2 study evaluating their combination in patients with platinum-treated, advanced UC (NCT03824691). Herein, we report the results of the planned interim safety analysis and the preliminary activity. PATIENTS AND METHODS: Patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1, UC and non-UC histology, and failure of a maximum of two regimens received cabozantinib 40 mg daily, orally, in combination with durvalumab 1500 mg, intravenously, every 28 days. Response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 every two cycles and by fluorodeoxyglucose positron emission tomography (FDG-PET) scans. RESULTS: As of August 20, 2020, 16 patients were enrolled with a median follow-up of 6.7 months (range, 2-11). Four patients (25%) had ECOG PS 1 and had received two prior regimens. No grades 3 or 4 treatment-related adverse events (TRAEs) occurred within the first two cycles. The most common grades 1 and 2 TRAEs were fatigue (7, 43.8%), diarrhea (5, 31.3%), and dysphonia (5, 31.3%). Objective responses were seen in six patients (37.5%; 95% confidence interval, 15.2-64.6), including two complete responses (12.5%). One additional patient with bone-only disease obtained a decrease in FDG uptake and in circulating tumor DNA consistent with response. Angiogenesis-related gene alterations were found in 57% responders versus 0% nonresponders. CONCLUSION: The durvalumab and cabozantinib combination was safe and endowed with preliminary clinical activity in patients with advanced UC. Mature results will clarify the role of cabozantinib and that of tumor biomarkers in this tumor type.

Does the administration of preoperative pembrolizumab lead to sustained remission post-cystectomy? First survival outcomes from the PURE-01 study☆.

BACKGROUND: Initial studies of preoperative checkpoint inhibition before radical cystectomy (RC) have shown promising pathologic complete responses. We aimed to analyze the survival outcomes of patients enrolled in the PURE-01 study (NCT02736266). PATIENTS AND METHODS: We report the results of the secondary end points of PURE-01 in the final population of 143 patients. In particular, we report the event-free survival (EFS) outcomes, defined as the time from the first cycle of pembrolizumab to radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy (NAC), recurrence after RC, or death from any cause. Other end points were recurrence-free survival (RFS) and overall survival (OS). Subgroup analyses were carried out, including pathological response category, clinical complete responses (CR) assessed via multiparametric magnetic resonance imaging (mpMRI), and molecular subtyping. Cox regression analyses for EFS were also carried out. RESULTS: After a median [interquartile range (IQR)] follow-up of 23 (15-29) months, 12- and 24-month EFS were 84.5% [95% confidence interval (CI): 78.5-90.9] and 71.7% (62.7-82). The prognosis was favorable across all the different pathological response subgroups, with the exception of ypN+ (N = 21), showing a 24-month RFS (95% CI) of 39.3% (19.2% to 80.5%). A statistically significant EFS benefit was observed in patients with a clinical CR (P = 0.002). Programmed cell-death-ligand-1 combined positive score was significantly associated with longer EFS in multivariable analyses. Four patients refused RC after clinical evidence of CR, and none of them have recurred after a median follow-up of 10 months (IQR: 11-15). The claudin-low subtype displayed a numerically longer EFS after pembrolizumab and RC compared with the other subtypes. CONCLUSIONS: The EFS results from PURE-01 revealed that the immunotherapy effect was maintained post-RC in most patients. Pembrolizumab compared favorably with neoadjuvant chemotherapy, irrespective of the biomarker status. Molecular subtyping may be a useful tool to select the patients who are predicted to benefit the most from neoadjuvant pembrolizumab.

Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study.

BACKGROUND: Pembrolizumab is a new standard of care for patients with platinum-treated, metastatic urothelial carcinoma (UC). Nab-paclitaxel is active in advanced UC. In the PEANUT study (NCT03464734) we investigated their combination in advanced UC. PATIENTS AND METHODS: PEANUT was an open-label, single-arm, phase II trial that included patients who had failed one or two chemotherapy regimens, including platinum chemotherapy. Biomarker analyses focused on programmed cell-death ligand-1 combined positive score (CPS) and comprehensive genomic profiling on tumor samples and circulating tumor DNA. Patients received 200 mg pembrolizumab on day 1 (D1), and 125 mg/m2 nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) according to RECIST (v1.1). The assumption was to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). RESULTS: Between January 2019 and January 2020, the PEANUT study enrolled 70 patients: 24% had failed two prior systemic therapies; 31% had an Eastern Cooperative Oncology Group (ECOG) performance status of 1; and 28.6% had liver metastases. After a median follow-up of 9.8 months, 40 patients have relapsed (57.1%). The median PFS was 5.9 months [95% confidence interval (CI) 3.1-11.5]. The confirmed objective response rate (ORR) was 38.6% (95% CI 27-51) with 17 partial responses and 10 complete responses (14.3%). The median duration of response was not reached. Five patients (7.1%) had ongoing responses lasting >12 months. The most common any-grade treatment-related adverse events included alopecia (71.4%), neutropenia (32.9%), and peripheral neuropathy (34.3%). Neither tumor mutational burden nor CPS was significantly associated with PFS at univariable analyses. The single-arm design of the trial was the major limitation. CONCLUSIONS: Pembrolizumab combined with nab-paclitaxel, as second- and third-line chemoimmunotherapy for metastatic UC, showed a favorable safety profile, durable PFS, and a clinically meaningful ORR in these preliminary analyses. This combination warrants additional randomized studies in earlier disease stages. CLINICALTRIALS. GOV NUMBER: ClinicalTrials.govNCT03464734; https://clinicaltrials.gov/ct2/show/NCT03464734.

Enrico Sertoli and the supporting cells of the testis "Morphology is function".

In 1865, Enrico Sertoli, at the age of 23, published an article in his own name entitled: "About the existence of special branched cells in the seminiferous tubules of the human testis". These were Sertoli's ideal cells; in this paper he arrived at a perspicacious description of the morphology and function of these cells and in the subsequent articles he investigated the topic of spermatogenesis. Despite the importance of Sertoli's discovery, the attention of the scientific literature remained very limited after Sertoli's death for half a century and the partial eclipse finished only in the 1970s of the twentieth century.

Pazopanib in advanced germ cell tumors after chemotherapy failure: results of the open-label, single-arm, phase 2 Pazotest trial.

Background: Therapeutic options for patients with chemoresistant germ cell tumors (GCTs) are limited. Pazopanib is a selective tyrosine kinase inhibitor with distinct antiangiogenic activity. We aimed to evaluate pazopanib activity in patients with refractory GCT. Patients and methods: In the open-label, single-arm, phase 2 Pazotest study (NCT01743482), patient eligibility included failure of ≥2 platinum-based regimens, and allowed prior high-dose chemotherapy administration. Patients were given pazopanib 800 mg/day until disease progression (PD) or onset of unacceptable toxicity. Measurements of serum tumor markers (STM), computed tomography and FDG-PET were carried out at baseline, after 4 weeks of pazopanib treatment, and every 8 weeks thereafter. PD was defined as increasing levels of STM, increasing size of non-teratomatous masses, or appearance of new lesions. The study primary endpoint was progression-free survival (PFS, H0: 3-month PFS ≤ 10%, H1: ≥25%, α = 5%, ß = 20%). Results: Forty-three patients were enrolled from May 2013 to July 2016. The number of prior chemotherapy regimens was: 2 (11.6%), 3 (51.2%), >3 (37.2%). Grade 3 adverse events were observed in six patients (13.9%). Overall, 70.3% of patients had reduced levels of STM after 4 weeks. There were 2 partial responses (4.7%), 19 cases of stable disease, and 16 cases of PD (6 not evaluable by RECIST). The median follow-up duration was 29.6 months. The 3-month PFS probability was 12.8% [95% confidence interval (CI): 5.7%-28.9%]. The 24-month OS probability was 14.2% (95% CI: 6.0%-33.7%). In patients with a >50% decline in STM, the 24-month OS probability was 24.1% (95% CI: 8.3%-69.6%). The small sample size was the major limitation. Conclusions: Despite pazopanib showed potent but short-lived activity in refractory GCT, long-term survival was obtained in a proportion of treated patients. According to the kinetics of pazopanib activity, this drug may be investigated in less pre-treated patients as an optimal bridging therapy preceding and/or combined with salvage chemotherapy.

miR-205 regulates basement membrane deposition in human prostate: implications for cancer development.

The basement membrane (BM) is a layer of specialized extracellular matrix that surrounds normal prostate glands and preserves tissue integrity. Lack or discontinuity of the BM is a prerequisite for tumor cell invasion into interstitial spaces, thus favoring metastasis. Therefore, BM maintenance represents a barrier against cancer development and progression. In the study, we show that miR-205 participates in a network involving ΔNp63α, which is essential for maintenance of the BM in prostate epithelium. At the molecular level, ΔNp63α is able to enhance miR-205 transcription by binding to its promoter, whereas the microRNA can post-transcriptionally limit the amount of ΔNp63α protein, mostly by affecting ΔNp63α proteasomal degradation rather than through a canonical miRNA/target interaction. Functionally, miR-205 is able to control the deposition of laminin-332 and its receptor integrin-ß4. Hence, pathological loss of miR-205, as widely observed in prostate cancer, may favor tumorigenesis by creating discontinuities in the BM. Here we demonstrate that therapeutic replacement of miR-205 in prostate cancer (PCa) cells can restore BM deposition and 3D organization into normal-like acinar structures, thus hampering cancer progression.

Assessment and reporting of pathological findings of penile specimens.

The correct assessment of penile specimens may provide clinically relevant diagnostic and prognostic data. This protocol is intended to assist pathologists in providing useful information to the clinicians and urologists and to uniform the examination of the penis by a standardized approach.

Atypical pleomorphic epithelioid angiomyolipoma localized to the pelvis: a case report and review of the literature.

AIMS: Angiomyolipoma is the most common mesenchymal tumour of the kidney. It has been reported in several other sites outside the kidney, mainly in the liver. We report the first case of atypical pleomorphic angiomyolipoma in a man, arising from the pouch of Douglas and extending to the entire abdominal cavity. METHODS: A 17-year-old man underwent a complete resection of a giant abdominopelvic mass. The tissue was formalin fixed and paraffin embedded and 4 micro m thick histological sections were stained with haematoxylin-eosin. Immunohistochemical stains for HMB-45, smooth muscle actin, vimentin, calponin, S100 and desmin were performed. Sections for electron microscopy were also prepared. RESULTS: Microscopic examination revealed a neoplasm composed of pleomorphic epithelioid cells with atypical features, immunoreactive for HMB-45, MART-1, actin, vimentin and calponin, while S100 protein and desmin stains were negative. Ultrastructurally, the tumour cells showed prominent nucleoli, vacuolated cytoplasm, and some premelanosomes. A diagnosis of atypical pleomorphic epithelioid angiomyolipoma was then made. CONCLUSIONS: To date five patients with abdominal epithelioid angiomyolipoma have been described in the literature. All were women. Three of the five patients reported developed metastasis, while our patient is still free of disease at 16 months of follow-up. Clear prognostic pathological features have not been identified.

Chordoma: natural history and results in 28 patients treated at a single institution.

BACKGROUND: The natural history of chordoma is characterized by a high failure rate and a poor functional outcome. The purpose of this study was to review the long-term outcome of our institutional experience. METHODS: The clinical features, type of treatment, pathologic assessment, and follow-up of 56 consecutive patients with chordoma were reviewed. RESULTS: Fifty sacral and six mobile spine chordomas (median size, 13 cm; range, 2-30 cm) were treated at our center between January 1933 and December 2000. Twenty-eight patients affected by sacrococcygeal chordoma and operated on after 1977 form the basis of our study. Surgical margins were rated as wide in 11 cases, marginal in 13 cases, and intralesional in 4 cases. The median follow-up was 71 months (range, 15-200 months). Seventeen patients' disease recurred. Ten patients died as a result of disease. Nine patients remained continuously free of disease. The estimated 5- and 10-year overall survival was, respectively, 87.8% and 48.9%; disease-free survival was 60.6% and 24.2%. Radiotherapy was considered for marginal and intralesional resections. CONCLUSIONS: High sacral amputation can achieve a good rate of wide-margin resections for sacrococcygeal chordomas. Adjuvant radiotherapy may offset the negative effect in the prognosis of marginal resections.

Quality of surgery and outcome in extra-abdominal aggressive fibromatosis: a series of patients surgically treated at a single institution.

PURPOSE: To explore prognostic factors in surgically treated aggressive fibromatosis (extra-abdominal desmoid tumor). PATIENTS AND METHODS: A total of 203 consecutive patients treated with surgery over a 35-year period at a single referral center were retrospectively reviewed. One hundred twenty-eight were first seen at our institution with primary disease, whereas 75 had a recurrent tumor. All patients underwent macroscopically complete resection. Margins were rated as negative in 146 (97 with primary tumors, 49 with recurrences) and positive in 57 (31 in primary, 26 in recurrences) patients. Median follow-up was 135 months. RESULTS: Patients with primary disease had a better disease-free survival rate than those with recurrence (76% v 59% at 10 years). Presenting with a recurrence was also the strongest predictor of local failure in the multivariate analysis. In patients first treated for primary disease, size and site had prognostic significance, whereas microscopically positive surgical margins did not. In contrast, in patients with recurrence, there was a trend toward better prognosis if margins were negative (although this was not significant at multivariate analysis). CONCLUSION: Presence of microscopic disease does not necessarily affect long-term disease-free survival in patients with primary presentation of extra-abdominal desmoid tumors. Thus, function-sparing surgery may be a reasonable choice when feasible without leaving macroscopic residual disease. In patients with recurrences, positive margins may more clearly affect prognosis, potentially necessitating adjuvant radiation in selected cases.

Immunohistochemical and quantitative study of mast cells in La Peyronie's disease.

OBJECTIVE: In order to investigate the possible association between mast cells (MCs) and the fibrous plaque of La Peyronie's disease, the number of MCs in normal penile tissue and in the fibrous plaque was determined. METHODS: The control group consisted of 5 total and 3 partial penectomies with no fibrotic lesions, while the study group consisted of 23 excisional biopsies from cases of La Peyronie's disease dating back to at least 2 years earlier and with no signs of activity. The biopsies included tissues from the tunica albuginea (TA), the areolar tissue (Br) between the tunica and the erectile tissue (CC) and from the latter. The number of MCs was counted with the aid of an image analysis program following staining the antibody antitryptase. RESULTS: In the cases of La Peyronie's disease the number of MCs/mm(2) was significantly higher in the TA and Br but lower in the CC. The MCs were related to fibroblasts and vasculonervous channels in the TA, and were concentrated around the fibrous plaques and granulation tissue between the TA and BR and between the latter and the CC. CONCLUSION: Our data indicate that MCs have a role in the genesis of the fibrous plaque in the TA and in the persistent inflammation in the Br. Medical treatment aimed at repressing MC activation and proliferation locally might be useful in La Peyronie's disease.

Sudden death in a child due to rare endocranial neoformation.

A case of unexpected death in a six-year-old child, who died after a period of non-specific symptoms and clinical signs, is described. The cause of death was a pilocytic astrocytoma of the pontocerebellar angle, rare with regard to location and histology. The authors have reviewed the literature, which was scanty.

Detection of apoptosis by the TUNEL technique in clinically localised prostatic cancer before and after combined endocrine therapy.

AIMS: Apoptosis in prostate cancer was evaluated after three months of combined endocrine therapy to investigate the association with tumour grade, tumour stage, and the immunohistochemical detection of p53 and bcl-2 in tumour cells before and after therapy. METHODS: Twenty six formalin fixed, paraffin wax embedded core biopsies and corresponding prostatectomy specimens, excised after three months of combined endocrine therapy, were analysed for the presence of apoptotic cells by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method, and for p53 and bcl-2 overexpression by immunohistochemistry. RESULTS: All 26 adenocarcinomas were clinically localised at diagnosis. In biopsies performed before combined endocrine therapy, the apoptotic indices varied between 0.09% and 1.73%, while the tumour grade fell between Gleason score 1 and 8. The mean (SD) apoptotic count pretherapy was 0.71% (0.50). There was a significant association between elevated apoptotic counts and higher Gleason scores in the biopsies (p = 0.005). After three months of therapy, the percentage of apoptotic tumour cells increased independently of tumour stage, while a significant association with Gleason grade was found (p = 0.0018) and all the tumours had Gleason scores of < 7. In eight cases the apoptotic index was more than twice its pretherapy value. The remaining tumours showed less of an increase in the apoptotic index (five cases) or a reduction in the percentage of apoptotic cells. The overall moderate increase in apoptotic index after combined endocrine therapy was not statistically significant (p = 0.8). Immunoreactivity to p53 was absent in all cases, before and after therapy, while a slight increase in the number of cells overexpressing bcl-2 was observed in five of the 13 tumours (38.1%) with reduced apoptotic indices after therapy. CONCLUSIONS: After three months of combined endocrine treatment a minority of clinically localised prostate neoplasms showed regressive epithelial alterations, associated with an increase in apoptotic tumour cells; an increase in cells overexpressing bcl-2 was observed in five of the 13 tumours with reduced apoptotic indices.

Salivary duct carcinoma of the parotid gland. Report of a case with cytologic and immunocytochemical findings on fine needle aspiration biopsy.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare high grade neoplasm arising from the larger ducts of the major salivary glands, most frequently in the parotid glands in the elderly. It is important to identify some characteristics that allow differentiating SDC from the other salivary gland adenocarcinomas, which have different prognoses. CASE: A 63-year-old, white male presented with an indolent swelling in the left parotid gland, the retromandibular angle. Fine needle aspiration biopsy (FNAB) showed polygonal or cuboidal, medium-sized, moderately pleomorphic cells with round to oval nuclei in cytocentrifuge preparations. Small tissue fragments with a prominent cribriform pattern and an area of comedocarcinoma were observed in the cytocentrifuged material. Tumor cells were diffusely immunoreactive for low- and high-molecular-weight cytokeratins, and strong positivity was observed with 115D8 and Ber-EP4 antibodies. Overexpression of c-ERB B-2 was absent, and < 5% of the nuclei were immunoreactive for p53. CONCLUSION: The cytologic and immunocytochemical appearance of SDC are characteristic, and FNAB results provide the surgeon with useful information for planning surgical therapy.

[Hyperfunctioning thyroid carcinoma. Description of a case]. / Carcinoma tiroideo iperfunzionante. Descrizione di un caso.

Differentiated thyroid cancers account for 1% of all neoplasias but only for 2.3% of thyroid nodules. A particular condition is represented by the association with hyperthyroidism, which is found in about 7% of cases. Even more rarely may be themselves cause of thyrotoxicosis. In the present paper, the case of a 66-year old male patient, bearing a recently appeared goiter, referred to us for suspicion of lung cancer and hyperthyroid symptoms, is reported. Among appropriate investigations, the finding of high titer of thyroglobulin in the aspiration needle and cytology examination suggested that thyroid lesion was primary and not metastatic, while scintiscan with J-131 isotope showed that excess of thyroid hormones was just due to it; histological diagnosis was of papillary carcinoma. As to the pathogenesis of the neoplasma during hyperthyroidism, a causal role of thyroid stimulating auto-antibodies has been suggested in the cases associated with Graves' disease, absent in our patient, which could elicitate cancer progression in the mean time. Interestingly, activating mutation of thyroid hormone receptor (TSH-r) gene has been demonstrated in a hyperfunctioning differentiated cancer. Notwithstanding the unexpected clinical behaviour may appear very rare, molecular biology studies on aspiration biopsies (FNAB) will allow, in the future, to better define the neoplastic nature of some hot nodules. In personal opinion, this particular pathology must be attently searched both for its implications in the prognosis and therapeutic strategy and because it could be less rare than generally considered up to now.

Malaric placentas. A quantitative study and clinico-pathological correlations.

A histological and morphometric study was conducted on 372 placentae out of a total 440 delivered in Zanzibar. Fibrin (F), intervillous space (IVS) and Villi (V) relative volumes were determined by the point-counting system and the ratio of syncytium to blood capillaries by the linear intercept method. Parasitemia load and inflammatory reaction were graded semiquantitatively by the use of a 1 mm square grid. Parasitised red cells identified active malaria (AM), the presence of malarial pigment only identified past malaria (PM), and the absence of both characterized non-malarial placentae (NM). AM(17.87%), PM(21.61%) and NM(60.52%) placentae did not vary significantly in weight. Newborns from AM had a significantly lower weight than those from PM and NM. Peripheral and placental parasitemia were not coincident. Placental parasitemia load increased parallel with birthweight. The latter decreased with the increasing severity of the inflammation, particularly with the prevalence of lymphocytes in the IVS. Significantly increased volume of F was found in AM and PM placentae, while no significant variation was noticed in IVS and V volumes. The syncytium/capillaries ratio was significantly increased in AM. We conclude that low birthweight in malaria is linked to IVS inflammation but not to F deposits or parasitemia load. Non-leukotactic lymphokines might play some role. Morphologic aspects bespeak for a less mature placenta than expected and this might represent an adaptive change.

Different effects of calcitriol and parathyroidectomy on the PTH-calcium curve in dialysis patients with severe hyperparathyroidism.

BACKGROUND: The PTH-calcium sigmoidal curve is shifted to the right, the slope of the curve is steeper, and the set point of calcium is increased in dialysis patients with secondary hyperparathyroidism, compared to patients with low-turnover bone disease. These findings could be related to increased parathyroid cell mass and increased sensitivity of parathyroid cells to serum calcium variations in these patients. Calcitriol therapy has been documented to reduce PTH levels by shifting the curve to the left and downward. The effect of a surgical reduction of parathyroid gland mass on the PTH-calcium curve has not yet been investigated. In this study we compared the effects of calcitriol and subtotal parathyroidectomy (PTH) on the dynamics of PTH secretion in response to acute changes of serum calcium in two groups of dialysis patients with severe hyperparathyroidism. METHODS: Fourteen dialysis patients treated for 6 months with high-dose i.v. calcitriol (1-2 micrograms thrice weekly, and 10 dialysis patients who underwent subtotal PTx were studied. The PTH-calcium relationship obtained by inducing hypo- and hypercalcaemia means of low and high calcium dialysis was evaluated before and 2-6 months after treatment. RESULTS: Both calcitriol and subtotal PTx significantly decreased PTH (respectively from 797 +/- 595 to 380 +/- 244 and from 1036 +/- 250 to 70 +/- 34 pg/ml), as well as maximal PTH response to hypocalcaemia (PTHmax), and maximal PTH suppression during hypercalcaemia ( PTHmin). When the PTH-calcium curves were constructed using PTHmax as 100% to factor for differences in absolute PTH levels and to provide an assessment of individual parathyroid cell function, a shift of the sigmoidal curve to the left and downward, and a significant decrease in the set point of ionized calcium (from 1.31 +/- 0.05 to 1.26 +/- 0.05 and from 1.36 +/- 0.09 to 1.22 +/- 0.07 mmol/l) was documented with both treatments. However, the slope of the PTH-calcium curve increased after subtotal PTx indicating that the sensitivity of the parathyroid cell to serum calcium changes increased with PTx, while on the contrary it decreased with calcitriol. CONCLUSIONS: PTH secretion decreases proportionally more with calcitriol than with surgery for a given decrease in the functional mass of parathyroid cells. The change in the PTH-ICa sigmoidal curve induced by subtotal PTx is due to the removal of a large mass of parathyroid tissue with advanced hyperplasia.

p53 protein expression in fine-needle aspirates of breast cancer: an immunocytochemical assay for identifying high-grade ductal carcinomas.

The expression of the p53 gene product was investigated immunocytochemically in a series of 51 fine-needle aspiration (FNA) samples of breast carcinomas. Results were compared with those obtained by immunocytochemically on paraffin embedded tissue sections of the corresponding surgical specimens. Cytological samples showed a variable degree of p53 immunoreactivity in 14 tumors (27.6%), all of ductal type, while p53 immunoreactive tumor cells were present in tissue sections from 15 carcinomas (29.4%). The only discordant case was a signet-ring cell carcinoma. Abnormal p53 expression was significantly associated with high nuclear grade in ductal carcinomas. No association was seen with tumor size, lymph node status, and age of the patient. Detection of p53 altered expression in FNA samples of breast carcinoma may play a role in the assessment of tumoral grading and is predictive of p53 immunoreactivity in histological specimens.