Roberto Cocchi

Pattern of p63 expression in squamous cell carcinoma of the oral cavity.

P63 is a recently discovered gene harbouring different isoforms by alternate splicing. The two main isoforms, TAp63 and ΔNp63, have opposite functions, being responsible for cell-cycle arrest and cell proliferation, respectively. In addition, new isoforms have been described with the same sequence as TAp63 and ΔNp63, but lacking exon 4 (Δ4Tap63 and ΔNp73L). P63 as detected using immunohistochemistry is present in squamous cell carcinomas. To better define the role of p63 in squamous cell carcinomas of the oral cavity (OSCC), 39 patients were investigated using immunohistochemical analysis with a monoclonal antibody recognising all p63 isoforms and an anti-Ki67 antibody. Reverse-transcription polymerase chain reaction (PCR) and nested PCR were also performed using isoform-specific primers to evaluate the p63 mRNA expression pattern. Using immunohistochemistry, p63 was always present in OSCC, and its distribution was similar to that of Ki67. The percentage of positive cells increased from normal to neoplastic mucosa, but there was no relationship between the number of p63 positive cells and prognosis. P63 mRNA was found in all patients. The truncated isoforms Δ4TAp63 and ΔNp73L were more frequently expressed in patients presenting with metastases. ΔNp73L was found in 66.6% of tumours with lymph-node metastases, but in only 33.3% of those devoid of lymph-node metastases at presentation. An impaired expression of the p63 isoforms might favour cell proliferation and indirectly enhance the metastasising capacity of OSCC.

E-cadherin loss and ΔNp73L expression in oral squamous cell carcinomas showing aggressive behavior

This article sought to investigate the existence of parameters useful for predicting lymph node metastases in cases of surgically resected oral squamous cell carcinomas (OSCCs).

p63 Expression in Salivary Gland Tumors: Role ofΔNp73L in Neoplastic Transformation

To illustrate the role of p63 and its truncated variants in salivary gland tumors, 23 consecutive tumors and 6 normal salivary glands were studied immunohistochemically with anti-p63 antibody and by reverse transcriptase (RT) and nested polymerase chain reaction (PCR) to detect p63 isoform expression. Normal salivary glands: p63 antibody-stained basal and myoepithelial cells; by RT and nested PCR, the 2 main isoforms were present, whereas ΔNp73L was absent. Tumors: p63 antibody was positive in the following: Warthin tumor (WT) (3/3), oncocytoma (OC) (1/1), pleomorphic adenoma (PA) (7/7), polymorphous-low-grade adenocarcinoma (PLGA) (3/3), adenoid-cystic carcinoma (ADCC)(3/4), epithelial-myoepithelial-cell carcinoma (EMC) (1/1), and myoepithelial-cell carcinoma (MCC) (1/1). By RT and nested PCR all tumors expressed p63 irrespective of their morphologic differentiation. The ΔNp73L isoform was present in tumoral tissue but absent in normal salivary gland. These data suggest that p63, particularly its splice variant ΔNp73L, is involved in the neoplastic transformation of salivary glands.

Hemimandibular hyperplasia: treatment strategies.

Hemimandibular hyperplasia is a well-defined, rare asymmetrical mandibular malformation. It is characterized by diffuse enlargement of the condyle, the condylar neck, and the ramus and body of the mandible. Because the anomaly begins before puberty, it is understandable that the maxilla follows the downward growth of the mandible. Pathogenesis is due most likely to clear hyperactivity in the condyle, which can be documented histologically with an actively proliferating cartilage. Therapy is largely based on the patients age. The authors present their series of nine individuals with hemimandibular hyperplasia treated with various surgical methods between 1992 and 1994. A therapeutic approach called orthopedic maxillary management applied to two of the nine patients is presented. The objective is to maintain the occlusal maxillary plane in a correct position in growing patients. All clinical results, except one, were satisfying and showed good postoperative stability.

Cancerization of cutaneous flap reconstruction for oral squamous cell carcinoma: report of three cases studied with the mtDNA D-loop sequence analysis

Foschini M P, Morandi L, Marchetti C, Cocchi R, Eusebi L H, Farnedi A, Badiali G, Gissi D B, Pennesi M G & Montebugnoli L
(2011) Histopathology58, 361–367
Cancerization of cutaneous flap reconstruction for oral squamous cell carcinoma: report of three cases studied with the mtDNA D‐loop sequence analysis

Podoplanin and E-cadherin Expression in Preoperative Incisional Biopsies of Oral Squamous Cell Carcinoma Is Related to Lymph Node Metastases

Metastases to cervical lymph nodes (LNs) are an important independent adverse indicator in the prognosis of oral squamous cell carcinoma (OSCC). An accurate evaluation of molecular patterns favoring the metastatic process can be helpful in predicting cases of OSCC with elevated probability of early or late metastases and, moreover, in planning the proper therapeutic procedures before surgery. To this end, immunohistochemical expressions of both E-cadherin and podoplanin were evaluated on preoperative incisional biopsies of OSCC from 102 patients. The probability to have or develop metastases was very low when high E-cadherin expression was found in a preoperative sample or when a low podoplanin expression was found. Therefore, because of the strong association with LN metastases, high E-cadherin/low podoplanin immunohistochemical expression should also be assessed on preoperative incisional biopsies as a useful tool for evaluating the probability of early or late LN metastases of OSCCs.

Immunohistochemical expression of p16INK4A protein as a helpful marker of a subset of potentially malignant oral epithelial lesions: study on a series with long-term follow-up

Montebugnoli L, Cervellati F, Cocchi R, Farnedi A, Pennesi M G, Flamminio F & Foschini M P
(2010) Histopathology57, 528–534
Immunohistochemical expression of p16INK4A protein as a helpful marker of a subset of potentially malignant oral epithelial lesions: study on a series with long‐term follow‐up

Orofacial Granulomatosis: Clinical Signs of Different Pathologies

Orofacial granulomatosis (OFG) is an uncommon disease characterized by persistent or recurrent soft tissue enlargement, oral ulceration and a variety of other orofacial features. It could be an oral manifestation of a systemic disease. For a correct differential diagnosis, local and systemic conditions characterized by granulomatous inflammation should be excluded using appropriate clinical and laboratory investigations. In fact, the diagnosis of OFG may be confirmed only by histopathological identification of noncaseating granulomas. The literature from 1943 to 2014 was reviewed with emphasis on the etiology of OFG and on clinical manifestations of systemic pathologies associated with OFG. The precise cause of OFG is still unknown, although several theories have been suggested, such as infection, hereditary factors and allergy. OFG is a disease that has a wide spectrum of presentation, which may include the oral manifestation of a systemic condition such as Crohns disease, sarcoidosis, granulomatosis with polyangiitis and Melkersson-Rosenthal syndrome.

Signet ring cell tumor of the minor salivary gland exhibiting benign behavior

Signet ring cell (SRC) carcinomas are usually aggressive malignancies, arising most frequently in the stomach and gastrointestinal tract, but also, although less often, in other organs such as the breast, bladder, and lungs. They are particularly unusual in the salivary glands, and the aim of the present study is to report a case of a tumor of the minor salivary glands of the lower lip composed largely of SRCs but which displayed benign clinical behavior.

Genetic relationship between multiple squamous cell carcinomas arising in the oral cavity.

Histological and clinical criteria are generally used to differentiate second primary tumors (SPTs) from local recurrences. The purpose of the present study was to apply mitochondrial DNA (mtDNA) D‐loop analysis to differentiate SPTs from local recurrences and to validate the clinical classification.