TROP-2 expression in papillary thyroid cancer: a preliminary cyto-histological study.

OBJECTIVE: TROP-2 (human trophoblast cell surface marker) is a gene-related protein expressed in trophoblastic cells, which is also present in a variety of epithelial cancers and whose overexpression has been found to correlate with a poor prognosis. We analysed the possibility of using the expression of TROP-2 to detect papillary thyroid carcinoma (PTC) on cytological and histological samples, and compared it with Hector Battifora mesothelial antigen-1 (HBME-1). METHODS: From 127 patients, 127 fine needle aspirates (FNAs), in which HBME-1 was detected by immunocytochemistry (ICC), were re-classified according to the Bethesda system for reporting thyroid cytopathology (TBSRTC): 20% were benign, 56% were atypical cells/follicular lesion of undetermined significance (AUS/FLUS), 4% were follicular neoplasm/suspicious for a follicular neoplasm, 5% were suspicious for malignancy and 16% were malignant. Sufficient material to test for TROP-2 was available in 64 FNAs, 22 of which had a histological control. Including six additional cases in which the FNAs were not available, immunohistochemistry (IHC) was carried out with both markers on 94 cases. RESULTS: Among 88 FNAs with histological control, the sensitivity of HBME-1 to predict PTC was 87.5% (28/32) and the specificity was 86% (48/56), whereas, in 22 FNAs, TROP-2 sensitivity was 100% (13/13) and specificity was 89% (8/9). In 94 histological specimens in which IHC was carried out with both markers, the sensitivity and specificity were 82% and 86%, respectively, for HBME-1 and 87% and 89%, respectively, for TROP-2. The difference between the markers was not significant. Concordance between IHC and ICC was 76% for HBME-1 and 91% for TROP-2. CONCLUSION: TROP-2 can be used as well as HBME-1 in thyroid cytology to detect PTC. Positivity for either or both markers could help to stratify the risk of malignancy in indeterminate FNAs. Larger studies are need to analyse its role in the behaviour of PTC and its variants.

Clinical aggressiveness of incidental and non-incidental thyroid cancer.

BACKGROUND: With the increasing use of thyroid ultrasound, the recognition of thyroid nodules in a large proportion of apparently healthy subjects has become common. Because also the papillary thyroid microcarcinomas (PTMC) are being increasingly discovered, it is important to ascertain whether PTMC may exhibit heterogenous clinical features, associated with different aggressiveness. AIM: We retrospectively examined 122 subjects [98 female (80.3%), and 24 male (19.7%)] with thyroid cancer to find potential clinical and pathological findings that could be predictive of clinically aggressive behavior. RESULTS: Twenty of the 31 patients with true incidental cancer (64.5%) in comparison to 20 of the 91 patients with non-incidental cancer (21.9%) had a diameter <10 mm, and this difference was statistically significant (p<0.0001). There was a statistically significant association between size and invasiveness because 19.3% of invasive cancers were <10 mm whereas 44.6% of non-invasive cancers were <10 mm (p=0.005). The relationship between incidental discovery and invasiveness was also evaluated, but the proportion of incidental invasive cancer (19.3%) was not significantly different from that of incidental non-invasive cancer (30.8%). In the multivariate analysis, only size <10 mm (odds ratio=0.35, p=0.013) and papillary vs other histotypes (odds ratio=0.35, p=0.04) were statistically significant protective factors against invasiveness. CONCLUSIONS: a) Incidentally discovered thyroid cancers are more frequently microcarcinomas; b) there appears to be no difference in terms of invasive behavior between incidental and non-incidental thyroid cancer; c) smaller tumor size emerges as a protective factor.

A possible role of thymidine phosphorylase expression and 5-fluorouracil increased sensitivity in oropharyngeal cancer patients.

Thymidine Pi deoxyribosyltransferase (TP) is an enzyme involved in DNA synthesis up-regulated in tumours and it is also a pro-angiogenic factor. TP cannot activate capecitabine, because capecitabine first needs conversion by carboxylesterase and cytidine deaminase into 5-deoxy-fluorouridine. This compound can be activated by TP to 5-fluorouracil (5-FU). Although TP is not necessary for 5-FU toxicity, experimental data suggest that high levels of TP correlate with an enhanced response to 5-FU therapy. In this study, we have analysed by immunohistochemistry CD34, CD68 and TP positive cells in bioptic samples from 53 patients with T(1-3) N(0-1) M(0) oropharyngeal squamous cell carcinoma (OSC) and from 24 patients with non-dysplastic oropharyngeal leukoplakia (NDOLP). Results showed that the mean of TP-positive cells, CD68 positive macrophages and CD34 positive endothelial cells eval-uated as microvessel density (MVD) was significantly higher in OSC than in NDOLP. Moreover, at a median follow-up of 19 months, patients with TP expression and higher MVD showed a better survival rate as compared to those with low MVD, probably as a consequence of 5-FU-based therapy.We hypothesized a role for TP in oropharyngeal tumourigenesis and 5-FU activation in the adjuvant setting of OSC patients.

[Biological-clinical significance of angiogenesis and mast cell infiltration in squamous cell carcinoma of the oral cavity]. / Significato biologico-clinico dell'angiogenesi ed infiltrato mastocitario nel carcinoma squamoso del cavo orale.

There are little data on the biological and prognostic role of neoangiogenesis in squamous cell carcinoma of the oral cavity (SCCOC). In particular, the role mast cells--reservoirs of angiogenetic peptides--play in neovascularization is not clear. In this work 50 cases of SCCOC T1-3 N0-1 M0 were studied, examining the microvasal density (MVD), mast cell density (MCD), relationship between these two parameters and their relationship with the pathological clinical features. Microvessels were identified with an immunohistochemical method using pan-endothelial anti-CD34 antibody while a histochemical method was used to label the mast cells with toluidine blue on adjacent sections for each tumor sample. MVD and MCD were characterized using an image analyzer. The mean MVD was 30 +/- 17 s.d. per sample while the average MCD was 8 +/- 6 s.d. per sample. Statistical analysis comparing MVD and MCD using the Pearson method showed a direct, significant correlation between the two variables (correlation coefficient = 0.496; p = 0.000). When the carcinomas were divided into subgroups with high and low MVD and MCD--using the median counts (27 and 7 respectively) as cutoff point--no association was found with the main clinical pathological features (age, sex, tumor diameter, lymph node status, cytopathological grading). As regards the correlation with prognosis, after an median 020 months of follow-up, the subgroup of patients with tumors with high MVD presented a better overall survival at 18 months from diagnosis than did the subgroup with tumors with a lower degree of vascularization (70% vs. 45%; p = 0.049 log rank test). The data obtained suggest that mast cells play an active role in angiogenetic processes in SCCOC and indicate that MVD is a favorable prognostic factor for SCCOC patients.

Primary tumours neoangiogenesis and P53 expression in oral carcinoma patients.

Paraffin embebbed tumour tissues from 47 T1-2 N0-1 M0 primary oral squamous carcinoma have been utilized for immunohistochemical analysis of p53 expression (moab DO-7) and microvessel density (MVD) analysis (moab CD34). Fifty percent of cases showed p53 immunostaining with an average of 21% of p53 positive cells. A strong trend for a longer survival in patients with tumor p53- versus p53+ was evidenced (median survival: 12 months versus not reached, respectively; p=0.08 by log-rank test). A mean value of 27 MVD was found. The probability of overall survival did not result significantly different in the subgroups of tumours with high and low MVD (median survival: 6 months versus 6 months, respectively; p=0.24). Cox multivariate analysis confirmed that the only prognostic factor significantly related to the overall survival was clinical nodal status (O.R.=2.7; 95% C.I. 1.09-6.9), while p53 status only approached the statistical significance (O.R.=2.5; 95% C.I. 0.96-6.5; p=0.06).

[Mandibular metastases from rectal adenocarcinoma: clinical case report and review of the literature]. / Metastasi mandibolare da adenocarcinoma del colon: descrizione di un caso clinico e revisione della letteratura.

A case is described of a 57-year-old woman with jaw metastasis from rectal adenocarcinoma who underwent colectomy and ovariectomy for moderately differentiated adenocarcinoma of the large intestine and peritoneal carcinosis. This patient subsequently underwent several cycles of chemoantiblastic therapy although, approximately six months after the initial surgery, a tumefaction of the gingival mucosa was found in the lower right premolar area. Radiography showed this neoformation to be an area of mandibular osteolysis. A biopsy, performed at the E.N.T Clinic of the IRCCS Oncological Hospital in Bari, Italy, revealed a metastatic lesion from rectal adenocarcinoma. This led to radiation therapy vs. the external fascia of the mandibular lesion. Then, given that further cerebral and hepatic metastases were found, palliative treatment was administered until the patient's death in June 2000. A review of the international literature shows how unusual it is to find secondary metastases from rectal adenocarcinoma in the mandibular region (only 23 cases have been published in the last forty years). For nearly all the authors examined, the treatment of choice for such lesions was radiation therapy associated with chemoantiblastic therapy. Despite such treatment, the literature bears significant agreement as to the poor, short-term prognosis.

Early, late symptoms and histological type of nasopharyngeal carcinoma.

After a wide literature review, we retrospectively analyzed the accurately recorded early onset and late symptoms at first diagnosis of nasopharyngeal carcinoma (NPC) in a series of 85 patients. Thirty-seven (44%) and 48 (56%) of cases had a squamous (SCC) and undifferentiated (UCNT) histological NPC subtype, respectively. Thirteen (15%), 21 (25%) and 51 (60%) of cases were T2, T3 and T4, respectively. The involvement of locoregional lymph nodes resulted significantly more frequent in UCNT with respect to SCC (35% versus 18% respectively; p<0.05). Overall, the early onset symptoms were represented by locoregional lymph node enlargement in 35% of cases; nasal symptoms in 32%, otological symptoms in 36%, while neurological symptoms were reported in only 2% of cases. On the contrary, symptoms at first diagnosis were more frequently represented by lymph node enlargement (53%) and nasal symptoms (68%) which were the symptoms effectively conducting the patients to the specialist. A protocol for management of ORL symptomatic patients according to the incidence of described early onset and at first diagnosis symptoms is suggested.

DNA flow cytometry, p53 levels and proliferative cell nuclear antigen in human colon dysplastic, precancerous and cancerous tissues.

BACKGROUND: The cancerogenic process of colorectal cancer depends on a series of events involving oncogenes and inactivation of suppressor genes. This study concerns changes in DNA content, p53 and PCNA expression in human colon in dysplastic, precancerous and cancerous tissues. MATERIALS AND METHODS: These characteristics were analyzed in a series of hyperplastic polyps (HP), adenomas (AD), adenocarcinomas evolved within adenomas (AC-AD) and adenocarcinomas (AC) of the large bowel. DNA ploidy was analyzed by flow cytometry and PCNA and p53 expression was evaluated by immunohistochemistry using monoclonal antibodies PC10 and PAb 1801. RESULTS: Aneuploidy was found in 43/67 (64%) of AC and only occasionally in other subgroups (AC vs all other groups: 64% vs 99%; p = 0.00002). PCNA positivity gradually increased in the sequence from HP to AC and were significantly higher in AC compared to HP (90% vs 44%; p = 0.00007). p53 positive cells were found in 67% of AC while only occasionally in other groups (HP vs AC: p = 0.0002, AD (low dysplasia) vs AC: p = 0.001; AD (moderate dysplasia) vs AC: p = 0.001). CONCLUSIONS: These results demonstrated a progressive immunoreactivity for PCNA in the HP to AC sequence, while p53 positivity and aneuploidy seemed specific for colon carcinoma.

[Cisplatin ototoxicity: the experience of the Institute of Oncology in Bari]. / Ototossicità da cisplatino: l'esperienza dell'Istituto Oncologico di Bari.

The Authors report their experience, developed in the E.N.T. Unit of the Oncologic Institute of Bari, concerning the ototoxic effect of Diamminedichloroplatinum (CDDP). The Study was carried out on 74 patients with advanced cancer of the head and neck, treated according to the polychemotherapeutic scheme called "MBD" in 34 cases and in 40 cases according to the scheme called "Al Sarraf". The otologic evaluation was composed, in all the cases, of a complete series of audio-vestibular investigation, carried out prior to and immediately after every administration chemotherapy and periodically, during a 4 months period after interruption of therapy. Three patients (4%) showed significative acoustical damage, none showed vestibular deficit. Symptoms did not appear beyond the second administration of CDDP, which always followed subjective acouphenic symptomatology. The ototoxic effect of CDDP, resulting in the experience of the Oncologic Institute of Bari, is percentually very low: and seems to be influenced by the single dose, rather than by the total doses and in any case is not preventable by any profilatic measure.

[Evaluation of nasal mucociliary activity in laryngectomized patients]. / Il comportamento dell'attività mucociliare nasale nei pazienti laringectomizzati.

The mucus-ciliar transport (M.C.T.) was studied by the indirect objective method of bleu of metilene in 30 patients undergone (at least since one year) on operation of total laryngectomy. The M.C.T. was absent in 1/3 of the patients and extended in almost all the others this kind of response may be explained as a consequence both of constitutional features and relative inertness of nasal mucous membrane following the absence of ventilation.

[Effect of topical exhedrine hydrochloride on muco-ciliary transport]. / Effeto dell'efedrina cloridrato per uso topico sul trasporto muco-ciliare.

The time of nasal M.C.T. (Mucus Ciliar Transport) was studied by the indirect objective method of bleu-sky in 30 healthy subjects before and after the application of efedrina hydrochloride in water solution associated with timolo, eucaliptolo, mentolo essence of canfora monobramata and clorbutamolo. The time of nasal M.C.T., regular in the 87% of the subjects during the first determination was found extended in almost all of the cases after the application of vasoconstrictor (85%). This experimental data may be caused both by a direct effect of efedrina hydrochloride and by the substances associated in the solution and their physical characteristics.