Nasopharyngeal carcinoma (NPC) is a central tumor with a rich lymphatic network and a propensity for bilateral cervical lymph node metastasis. There is an orderly pattern of lymph node involvement in NPC. There is no current standard for prophylactic neck irradiation in node-negative or limited retropharyngeal (RP) node-positive NPC. This study aims to synthesize the current evidence on upper neck irradiation (UNI) versus whole neck irradiation (WNI) as prophylactic neck irradiation in node-negative or limited RP node-positive NPC.

Anal intraepithelial neoplasia grade 2 (AIN2) and AIN grade 3 (AIN3) are commonly grouped together as high grade squamous intraepithelial lesions (HSIL). We assessed risk factors for HSIL-AIN2 and HSIL-AIN3 in a cohort of homosexual men.

Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV) and develops via precursor stages, called cervical intraepithelial neoplasia (CIN). High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1) increase our understanding of cervical carcinogenesis, 2) yield biomarkers for early diagnosis, and 3) identify therapeutic targets for HPV-induced (pre) cancerous lesions. This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.

We examined p16 expression in tumors from a population-based sample of laryngeal cancer cases diagnosed in the U.S. Samples had been previously genotyped for HPV DNA. Overall, p16 expression was observed in laryngeal tissue from 8 of 101 (7.9%) cases. p16 expression was observed in 2 of 16 (12.5%) cases previously determined to be HPV DNA positive. The two cases dually positive for p16 and HPV DNA were non-keratinizing SCC and papillary SCC tumors that were positive for genotypes 18 and 35/89, respectively. Positivity for p16 and/or HPV DNA was not associated with 5-year survival (log-rank p value= 0.55). Our findings support a limited role of HPV in laryngeal carcinogenesis. p16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival.

Intraosseous hibernoma is a rare benign bone tumor, with only 4 cases reported in English literature.

Cervical cancer is the second gynecological cancer Tunisian women after breast. This is a sexually transmitted disease including the role of HPV has been proven. Cervical cancer screening is possible due to the accessibility of the cervix with a speculum examination and implementation of cervical smear.

during this century, therapeutic management of rectal cancer has known a lot of advances. Survival is still depending on factors related to the patient, the tumor or the surgeon.

The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle.

Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR). All tissue and cfDNA samples underwent IonPGM sequencing for a CRC-specific 21-gene panel, which was analyzed using a standard and a modified calling pipeline. In addition, cfDNA, whole blood and normal tissue DNA were analyzed with the OnTarget assay and with dPCR for specific mutations in cfDNA as detected in the corresponding primary and/or metastatic tumor tissue. NGS with modified calling was superior to standard calling and detected ctDNA in the cfDNA of 10 patients harboring mutations in APC, ATM, CREBBP, FBXW7, KRAS, KMT2D, PIK3CA and TP53. Using this approach, variant allele frequencies in plasma ranged predominantly from 1 to 10%, resulting in limited concordance between ctDNA and the primary tumor (39%) and the metastases (55%). Concordance between ctDNA and tissue markedly improved when ctDNA was evaluated for KRAS, PIK3CA and TP53 mutations by the OnTarget assay (80%) and digital PCR (93%). Additionally, using these techniques mutations were observed in tumor-adjacent tissue with normal morphology in the majority of patients, which were not observed in whole blood. In conclusion, in these mCRC patients with oligometastatic disease NGS on cfDNA was feasible, but had limited sensitivity to detect all somatic mutations present in tissue. Digital PCR and mutant allele enrichment before NGS appeared to be more sensitive to detect somatic mutations.

The role of bone morphogenic protein 9 (BMP9) signaling in angiogenesis has been controversial, with a number of studies showing that it acts either as a pro-angiogenic or, conversely, as an anti-angiogenic factor in a context-dependent manner. Notably, BMP9 was also reported to function in both pro- or anti-tumorigenic roles during tumor progression. It has therefore remained unclear, whether selective BMP9 inhibition is a useful target for antibody therapy of cancer. To shed light on these questions, we characterized BMP9 expression in plasma of patients with different cancer indications and found elevated levels of pro-domains and precursor BMP9 with a strong response in renal cell carcinoma (RCC). These studies prompted us to evaluate the potential of selective anti-BMP9 cancer therapy in RCC. We generated a novel monoclonal therapeutic antibody candidate, mAb BMP9-0093, that selectively targets all different BMP9 variants but does not bind to the closest homolog BMP10. In vitro, mAb BMP9-0093 treatment inhibited signaling, endothelin-1 (ET-1) production and spreading of endothelial cells and restored BMP9-induced decrease in pericyte migration and attachment. Furthermore, BMP9-mediated epithelial-mesenchymal transition of renal cell carcinoma cells was reversed by mAb BMP9-0093 treatment in vitro. In vivo, mAb BMP9-0093 showed significant anti-tumor activity that was associated with an increase in apoptosis as well as a decrease in tumor cell proliferation and ET-1 release. Furthermore, mAb BMP9-0093 induced mural cell coverage of endothelial cells, which was corroborated by a reduction in vascular permeability, demonstrated by a diminished penetration of omalizumab-Alexa 647 into tumor tissue. Our findings provide new evidence for a better understanding of BMP9 contribution in tumor progression and angiogenesis that may result in the development of effective targeted therapeutic interventions.

Ovarian cancer is associated with poor survival, because patients are diagnosed at an advanced stage of the disease, and in addition, tumors develop chemoresistance, which carries a poor prognosis for the patient.

Cystic nephroma is a rare and benign renal tumour of unknown origin, usually diagnosed in the first years of childhood or during adult life. To our knowledge, there are no records in the literature of this particular tumour being descried prenatally. We present a case of a fetus diagnosed with cystic nephroma on 16 weeks of gestation. The renal tumour was evaluated by prenatal ultrasound, post mortem with 7T magnetic resonance imaging, and conventional autopsy.