Detection of CAF-1/p60 in peripheral blood as a potential biomarker of HNSCC tumors.

To date, a very small number of serum biomarkers have been identified for clinical use in squamous carcinomas of the head and neck region. Chromatin Assembly Factor-1 (CAF-1) heterotrimeric complex subunit CAF1/p60 expression levels have been reported to be of prognostic value in Oral Squamous Cell Carcinoma (OSCC), as well as in other human solid tumors. Here our aim was to detect and quantify CAF1/p60 in the peripheral blood of Head and Neck Squamous Cell Carcinoma (HNSCC) patients, and to investigate the possible associations between serum concentration of CAF-1/p60 and HNSCC tumors. A total of 63 HNSCC patients (51 OSCC, 8 OPSCC, 3 laryngeal SCC, and 1 rhinopharynx SCC) and 30 healthy controls were enrolled. The serum levels of CAF-1/p60 were measured by ELISA assay before and after surgery. Serum CAF-1/p60 concentration resulted significantly higher in cancer patients, compared with healthy controls, in pre-surgery samples (P < 0.05). Serum levels of CAF-1/p60 significantly decreased in serum samples taken after surgery (P < 0.05). Our results demonstrated that CAF-1/p60 may be detected in serum, suggesting a role for CAF-1/p60 as potential soluble biomarkers in HNSCC tumors.

A Machine-learning Approach for the Assessment of the Proliferative Compartment of Solid Tumors on Hematoxylin-Eosin-Stained Sections.

We introduce a machine learning-based analysis to predict the immunohistochemical (IHC) labeling index for the cell proliferation marker Ki67/MIB1 on cancer tissues based on morphometrical features extracted from hematoxylin and eosin (H&E)-stained formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples. We provided a proof-of-concept prediction of the Ki67/MIB1 IHC positivity of cancer cells through the definition and quantitation of single nuclear features. In the first instance, we set our digital framework on Ki67/MIB1-stained OSCC (oral squamous cell carcinoma) tissue sample whole slide images, using QuPath as a working platform and its integrated algorithms, and we built a classifier in order to distinguish tumor and stroma classes and, within them, Ki67-positive and Ki67-negative cells; then, we sorted the morphometric features of tumor cells related to their Ki67 IHC status. Among the evaluated features, nuclear hematoxylin mean optical density (NHMOD) presented as the best one to distinguish Ki67/MIB1 positive from negative cells. We confirmed our findings in a single-cell level analysis of H&E staining on Ki67-immunostained/H&E-decolored tissue samples. Finally, we tested our digital framework on a case series of oral squamous cell carcinomas (OSCC), arranged in tissue microarrays; we selected two consecutive sections of each OSCC FFPE TMA (tissue microarray) block, respectively stained with H&E and immuno-stained for Ki67/MIB1. We automatically detected tumor cells in H&E slides and generated a "false color map" (FCM) based on NHMOD through the QuPath measurements map tool. FCM nearly coincided with the actual immunohistochemical result, allowing the prediction of Ki67/MIB1 positive cells in a direct visual fashion. Our proposed approach provides the pathologist with a fast method of identifying the proliferating compartment of the tumor through a quantitative assessment of the nuclear features on H&E slides, readily appreciable by visual inspection. Although this technique needs to be fine-tuned and tested on larger series of tumors, the digital analysis approach appears to be a promising tool to quickly forecast the tumor's proliferation fraction directly on routinely H&E-stained digital sections.

FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?

Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors. We already investigated the role of the immune modulator FK506-binding protein 51 (FKBP51), a FK506-binding immunophilin, in cutaneous melanoma biology, and its expression in several human solid tumors. In the present study, we aimed to assess the value of FKBP51 expression in OSCC tumor cells as a marker of outcome. We collected clinical data from 72 patients who underwent surgery for Squamous Cell Carcinoma (SCC) of the tongue, floor, lips and palate. FKBP51 expression was assessed by immunohistochemistry on paraffin-embedded tumor tissues. In addition, we evaluated the human papillomavirus (HPV) status of primary tumors by immunohistochemistry, viral subtyping and In Situ Hybridization (ISH) assay. We found that high FKBP51-expressing tumors characterized the OSCCs with the worst prognosis: the high immunohistochemical expression of FKBP51 associated with death occurring within five years from the diagnosis with a sensitivity of 88.46% and a specificity of 91.67%. The estimated positive predictive value of the test was 88.45% and negative predictive value 91.67%. We tested FKBP51 mRNA presence, by RT-PCR assay, in a selected series of OSCC tumors, and we found that mRNA correlated well to the protein expression and to the clinical outcome. Applying the Bayes formula, we estimated an 88% probability of dying within five years from the diagnosis of OSCC patients with a high FKBP51 immunohistochemical (IHC) test result (>51% of FKBP51 positive tumor cells). On the basis of our analysis, we propose tumor tissue expression of FKBP51 protein as a reliable prognostic marker for OSCC tumors.

The "extended" endoscopic endonasal approach for the removal of a mixed intrasuprasellar germinoma: Technical case report.

BACKGROUND: Intracranial germ cell tumors (GCTs) represent less than 5% of pediatric brain tumors. Neurosurgical treatment remains essential in the management of patients with intracranial nongerminomatous GCT. CASE DESCRIPTION: A 12-year-old girl presented with clinical features of neurohypophyseal dysfunction and rapidly progressive visual worsening. Magnetic resonance imaging (MRI) showed a lesion arising from the sella with a significant suprasellar component, compressing the optic chiasm and extending into the third ventricle. The tumor was removed via an endoscopic endonasal transtuberculum-transplanum approach and the histology revealed a mixed germinoma. In the postoperative course, a conspicuous improvement of visual function was observed; an early postoperative MRI showed near-total removal of the lesion. The patient was referred to pediatric oncologist for the adjunctive chemotherapy and radiotherapy. CONCLUSIONS: The management of primary intracranial sellar and suprasellar germinomas still remains controversial. With this report we highlighted another possible surgical option among therapeutic strategies for these highly malignant tumors.