Follicular proliferation TIR3B: the role of total thyroidectomy vs lobectomy.

BACKGROUND: TIR3B thyroid nodules are considered to be at risk of malignancy (15-30%) but guidelines recommend conservative surgery with lobectomy with primary diagnostic porpoise. Risk stratification mainly based on ultrasound, elastography and genetic mutations usually may influences the surgical approach. METHODS: We retrospectively analyzed 52 cases of TIR3B underwent between 2015 and 2017 total thyroidectomy (TT) and lobectomy (L), focusing mainly on the observed rate of malignancy. Chi-squared test and Fisher's exact probability test were used for analysis, considering a P values less than 0.05 as significant. RESULTS: Out of 52 patients 49 underwent TT and 3 L. In TT group a multinodular goiter was associated in 67.3% of patients. Malignancy rate was 81.6 and 33.3% respectively after TT and L (P 0.003). Multicentric and contralateral tumors were detected respectively in 36.7% and in 32.6% of patients underwent TT. No main post-operative complications were registered. CONCLUSIONS: Ultrasound and elastography are useful to define within the TIR3B group those lesions at higher risk and therefore requiring a more radical approach. TT seems an appropriate approach to TIR3B lesions, especially in multinodular goiter, considering the incidence of malignancy with probably higher rate than previously reported.

XPG mRNA expression levels modulate prognosis in resected non-small-cell lung cancer in conjunction with BRCA1 and ERCC1 expression.

BACKGROUND: Molecular markers can help identify patients with early-stage non-small-cell lung cancer (NSCLC) with a high risk of relapse. Excision repair cross-complementing 1 (ERCC1), Xeroderma pigmentosum group G (XPG), and breast cancer 1 (BRCA1) are involved in DNA damage repair, whereas ribonucleotide reductase M1 (RRM1) is implicated in DNA synthesis. Expression levels of these molecules might therefore have a prognostic role in lung cancer. PATIENTS AND METHODS: We examined ERCC1, RRM1, XPG, and BRCA1 mRNA levels by real-time quantitative polymerase chain reaction in 54 patients with stage IB-IIB resected NSCLC. A strong correlation was observed between the 4 genes. RESULTS: For patients with low BRCA1, regardless of XPG mRNA expression levels, disease-free survival (DFS) was not reached. For patients with intermediate/high BRCA1 and high XPG, DFS was 50.7 months. However, for patients with intermediate/high BRCA1 and low/intermediate XPG, DFS decreased to 16.3 months (P = .002). Similar differences were observed in overall survival, with median survival not reached for patients with low BRCA1, regardless of XPG levels, or for patients with intermediate/high BRCA1 and high XPG. Conversely, for patients with intermediate/high BRCA1 levels and low/intermediate XPG levels, median survival dropped to 25.5 months (P = .007). CONCLUSION: BRCA1 and XPG were identified as independent prognostic factors for both median survival and DFS. High BRCA1 mRNA expression confers poor prognosis in early NSCLC, and the combination of high BRCA1 and low XPG expression still further increases the risk of shorter survival. These findings can help optimize the customization of adjuvant chemotherapy.

Ret/PTC activation does not influence clinical and pathological features of adult papillary thyroid carcinomas.

OBJECTIVE: RET proto-oncogene rearrangements (ret/PTCs) represent the most common genetic alterations found in papillary thyroid carcinomas (PTCs). Correlation of ret/PTC expression with clinical outcome is controversial. The aim of the present study was to analyze the frequency of RET rearrangements in adult PTCs, and to investigate if ret/PTCs influence biological behavior and clinical features of the cancers. DESIGN: Ret/PTC rearrangements were looked for in tIssue samples of 48 PTCs collected at our institution. Data about clinical and pathological features of the tumors were also reviewed. Three separate association analyses were carried out on the cohort evaluating the effects of, respectively, ret/PTC positivity, preferential RET tyrosine kinase domain (RET-TK) expression, and ret/PTC plus RET-TK positivity, on age, sex, tumor size, staging, number of neoplastic foci, and histological subtype. METHODS: The genetic study was conducted with the RT-PCR-Southern blot technique. Standard Student's t-test and Fisher exact test were applied for the association analyses. RESULTS: The molecular genetic study demonstrated the positivity of ret/PTC1 and ret/PTC3 in 13 of 48 tumors (27.1%), and an exclusive or preferential RET-TK expression in 17 cases (35.4%). None of the three genetico-clinical analyses showed any significant association between ret/PTC expression and the clinical and pathological features of the cancers. CONCLUSIONS: These data indicate that RET rearrangements may not play any distinctive role in driving histotype development and cancer progression in these neoplasms. Moreover, they weaken the possibility of using ret/PTC as a prognostic marker for papillary thyroid carcinomas.

Metaplastic carcinoma of the breast: Treatment, results and prognostic factors based on international literature.

Metaplastic carcinoma of the breast (MCB) is a rare form of cancer containing mixture of epithelial and mesenchymal elements in variable combinations. Few and conflicting clinical data are available in the literature addressing optimal treatment modalities, prognosis and outcome. A retrospective study was conducted to review all patients with MCB diagnosed and treated at Breast Unit of Azienda Ospedaliera "Santa Maria" Terni - Italy between 2001/2010. The aim is to describe patient's clinic pathologic features and to analyze treatment results. Six female patients were studied. The median age was 48 years (range 14/58). The median tumor size was 9 cm. (range 3/18 cm.). Two cases (33%) were identified as purely epithelial and 4 (67%) as mixed epithelial and mesenchymal metaplasia. Hormone receptors were positive in only 2 patients. Modified radical mastectomy performed in 3 patients and 5 underwent axillary node dissection. Adjuvant chemotherapy was given to all patients and postoperative radiotherapy to 4. Four patients relapsed with median time of relapse of 12 months. MCB is an aggressive form of breast cancer associated with poor outcome, high incidence of local recurrence and pulmonary metastases. The disease tends to be estrogen/progesterone receptor negative. Tumor size has an important impact on outcome. The best treatment approach is yet to be defined.

BRCA1: a novel prognostic factor in resected non-small-cell lung cancer.

BACKGROUND: Although early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage (IB, II, IIIA). Within each stage, gene expression profiles can identify patients with a higher risk of recurrence. We hypothesized that altered mRNA expression in nine genes could help to predict disease outcome: excision repair cross-complementing 1 (ERCC1), myeloid zinc finger 1 (MZF1) and Twist1 (which regulate N-cadherin expression), ribonucleotide reductase subunit M1 (RRM1), thioredoxin-1 (TRX1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T cells (NFAT), BRCA1, and the human homolog of yeast budding uninhibited by benzimidazole (BubR1). METHODOLOGY AND PRINCIPAL FINDINGS: We performed real-time quantitative polymerase chain reaction (RT-QPCR) in frozen lung cancer tissue specimens from 126 chemonaive NSCLC patients who had undergone surgical resection and evaluated the association between gene expression levels and survival. For validation, we used paraffin-embedded specimens from 58 other NSCLC patients. A strong inter-gene correlation was observed between expression levels of all genes except NFAT. A Cox proportional hazards model indicated that along with disease stage, BRCA1 mRNA expression significantly correlated with overall survival (hazard ratio [HR], 1.98 [95% confidence interval (CI), 1.11-6]; P = 0.02). In the independent cohort of 58 patients, BRCA1 mRNA expression also significantly correlated with survival (HR, 2.4 [95%CI, 1.01-5.92]; P = 0.04). CONCLUSIONS: Overexpression of BRCA1 mRNA was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set further strengthened this association. Since BRCA1 mRNA expression has previously been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 mRNA expression may provide additional information for customizing adjuvant antimicrotubule-based chemotherapy, especially in stage IB, where the role of adjuvant chemotherapy has not been clearly demonstrated.