The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16–1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26–2.02) and in studies using PCR (HR 1.40; 95% CI 1.18–1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86–1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

miRNAs Expression Analysis in Paired Fresh/Frozen and Dissected Formalin Fixed and Paraffin Embedded Glioblastoma Using Real-Time PCR

miRNAs are small molecules involved in gene regulation. Each tissue shows a characteristic miRNAs epression profile that could be altered during neoplastic transformation. Glioblastoma is the most aggressive brain tumour of the adult with a high rate of mortality. Recognizing a specific pattern of miRNAs for GBM could provide further boost for target therapy. The availability of fresh tissue for brain specimens is often limited and for this reason the possibility of starting from formalin fixed and paraffin embedded tissue (FFPE) could very helpful even in miRNAs expression analysis. We analysed a panel of 19 miRNAs in 30 paired samples starting both from FFPE and Fresh/Frozen material. Our data revealed that there is a good correlation in results obtained from FFPE in comparison with those obtained analysing miRNAs extracted from Fresh/Frozen specimen. In the few cases with a not good correlation value we noticed that the discrepancy could be due to dissection performed in FFPE samples. To the best of our knowledge this is the first paper demonstrating that the results obtained in miRNAs analysis using Real-Time PCR starting from FFPE specimens of glioblastoma are comparable with those obtained in Fresh/Frozen samples

Adenocarcinoma of the Lung Metastatic to the Ovary With a Signet Ring Cell Component

A nonsmoker 45-year-old woman, presented with a solid right ovarian mass. Microscopic examination revealed heterogeneous histology with tubular formations and extensive signet ring cell component that resembled the usual appearance of metastatic gastric carcinoma to the ovary. Moreover, the histology also showed solid nests of cells with a microvacuolated basophilic cytoplasm similar to those found in adenosquamous cervical carcinoma of glassy cell type. However, analysis of the patient's past history revealed a lung adenocarcinoma, diagnosed 4 years before, which prompted an immunohistochemical differential diagnosis, showing a strong expression for TTF-1 and Napsin A. A cervical primary was excluded taking into account both macroscopic findings and the negative expression of PAX8 and absence of human papillomavirus-related marker p16. This confirmed the pulmonary origin of ovarian tumor despite its heterogeneous morphology. This is the first reported case of ovarian metastatic lung adenocarcinoma, with a signet ring cell component and solid nests, mimicking both metastatic gastric carcinoma and adenosquamous carcinoma of glassy cell type

Clinico-pathological features of two new cases of Uterine Tumours Resembling Ovarian Sex Cord Tumours (UTROSCTs)

Uterine neoplasms showing an exclusive sex cord-like differentiation or focal low-grade sarcoma differentiation, designated as uterine tumors resembling ovarian sex cord tumors (UTROSCTs), are rare, with only 48 cases described earlier in international literature. Generally, this entity is characterized by benign behavior. In this study, we report the clinical and pathologic features of 2 peculiar new cases of UTROSCTs. In these examples, the pathologic diagnosis of UTROSCT was made incidentally after the clinical diagnosis of a leiomyoma and endometrial polyp. On examination of small biopsies, the diagnosis was facilitated by specific immunohistochemical analysis using markers for the sex cord component. In 1 of these cases, the patient, because of her young age and her desire to preserve her fertility, was only treated by minimally invasive hysteroscopic surgery. In the other case, the neoplasm seemed to be the consequence of tamoxifen treatment for breast carcinoma. After diagnosis, in this second case, the woman underwent hysterectomy that showed a residue of the tumor and cervical metastasis from the earlier breast carcinoma. The differential diagnosis of UTROSCT and the role of immunohistochemistry in confirming a diagnosis are discussed

The role of cervical smear in the diagnosis and management of extra-uterine malignancies metastatic to the cervix: Three case reports

ABSTRACT This report analyses the clinicopathologic features of three metastatic extragenital neoplasms to the cervix. These examples of metastatic extragenital malignancies to the cervix are cutaneous malignant melanoma, colorectal carcinoma, and breast carcinoma. The diagnosis of these metastatic malignancies was suspected on a historical basis. The value of Pap smears is limited on the other hand, since for a correct diagnosis in all our cases, this examination required corroboration by histological and immunohistochemical analysis. In all these examples of extragenital metastatic neoplasms, as in other cases reported in literature, the patients had undergone cervical smear because of vaginal bleeding, even if Pap smear is considered a questionable maneuver in vaginal bleeding. Accordingly, our article reveals that a great deal of rigorous screening, precise morphological analysis, and plentiful clinical data are mandatory in approaching diagnoses of extracervical malignancies. However, this study did demonstrate that cytology does not alter patient management or outcome. In effect, in accordance with other studies, our cases of metastatic extragenital neoplasms to the uterus have poor prognosis

Time trends of human papillomavirus type distribution in Italian women with cervical intraepithelial neoplasia (CIN)

OBJECTIVE: It is assumed that the circulation of HPV types in a population is stable over time although there are limited historical data to support this view. The existence of possible cohort effects in the circulation of HPV types has major implications for vaccination strategies and risk assessment in HPV-infected women. We analysed archival biopsy samples of cervical intraepithelial neoplasia (CIN) to study the distribution of HPV types in Northern Italy over the years 1985-2007. METHODS: DNA from formalin-fixed paraffin-embedded cervical biopsies from the years 1985-87 (67 samples) and 1995-97 (92 samples) was HPV-typed by the SPF-(10) Lipa assay. Cases were compared with 159 control biopsies from the years 2005-07 matched by patient age and CIN grade. Quantitative PCR was used to compare titres of HPV sequences in DNA extracted from biopsies of the three periods. Type-specific PCR was used to confirm HPV51 and 52 typing by SPF-(10) Lipa. RESULTS: HPV51, 52, 53, 56, 58, and 66 were markedly under-represented or undetectable in samples from past periods whereas they represented 5.7-30.8% of present infections. Frequency of multiple HPV infections and high-risk infections (p=0.0001) also increased in recent years. The main changes occurred over the last decade. Infections by HPV16, 18, were three times more frequent 20 years ago than today (p=0.012). Loss of amplifiable HPV sequences over prolonged storage was not observed. Type-specific PCR confirmed all HPV51 and 52 infections. CONCLUSIONS: Secular trends in the distribution of HPV types among women with CIN may occur in specific populations