Predictive markers of response to neoadjuvant therapy in rectal cancer.

BACKGROUND: Neoadjuvant therapy followed by radical surgery is the standard treatment in locally advanced rectal cancer. It is important to predict the response because the treatment has side effects and is costly. The aim of this study was to establish the relationship among clinical, pathologic, and molecular biomarkers and the response to neoadjuvant therapy. METHOD: A total of 130 patients with locally advanced mid and low rectal cancer who underwent long-course radiotherapy with 5-FU based chemotherapy followed by radical surgical resection were included in the study. Clinical and pathologic data were collected. Paraffin-embedded sections obtained in diagnostic biopsies were assessed by immunohistochemical staining for molecular markers and classified using a semiquantitative method. Results were related with T-downstaging and tumor regression grade using Mandard scoring system on surgical specimens. RESULTS: Pathologic complete response was found in 19 patients (14.6%), while in another 18 (13.8%) only minor residual disease was seen in the rectal wall. T-downstaging was observed in 63 (48.5%). The average of lymph node retrieval in the surgical specimens was 9.4. Regarding predictive markers of response, there was significant correlation between the expression of B-cell lymphoma 2 (P = 0.005), ß-catenin (P = 0.03), vascular endothelial growth factor (P = 0.048) and apoptotic protease activating factor 1 (P = 0.03), tumor differentiation grade (P < 0.001), and response in the univariate analysis. T-downstaging was associated with vascular endothelial growth factor expression (P = 0.03) and tumor differentiation grade (P < 0.001). Significant parameters found in the multivariate analysis were tumor differentiation grade and Bcl-2 expression. CONCLUSIONS: Pathologic and molecular biomarkers in the diagnostic biopsies may help us predict tumor response to chemoradiation in rectal cancer patients.

Sebaceous adenoma of the parotid gland.

Tumors of the salivary glands constitute an important field of oral and maxillofacial pathology. The majority of salivary gland neoplasms are benign, with malignant salivary tumors accounting for 15 to 32 percent. The most common site for salivary gland tumors is the parotid gland, accounting up to 80 percent of all cases. This article reports the pathologic picture in a case of sebaceous adenoma of the parotid gland. The tumor was composed of epithelial cells lining ducts and closely associated with broad areas of sebaceous differentiation. The growth pattern was predominantly cystic, with cavities filled with sebaceous material. Areas of oncocytic metaplasia were also seen. The presence of sebaceous glands in salivary neoplasms is frequent, however, and in spite of this, salivary neoplasms constituted partially or entirely of these cells are rarely observed. To the surgeon and pathologist, the major problem in dealing with sebaceous adenoma is the recognition of this rare entity, avoiding confusing with other more aggressive neoplasms. The treatment involves surgical excision. The addition of the current case to the previously published data brings the total number of parotid sebaceous adenoma to seven.

Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer.

PURPOSE: Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma. METHODS: An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up. RESULTS: An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%. CONCLUSION: These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma.

DNA methylation signatures identify biologically distinct thyroid cancer subtypes.

OBJECTIVE: The purpose of this study was to determine the global patterns of aberrant DNA methylation in thyroid cancer. RESEARCH DESIGN AND METHODS: We have used DNA methylation arrays to determine, for the first time, the genome-wide promoter methylation status of papillary, follicular, medullary, and anaplastic thyroid tumors. RESULTS: We identified 262 and 352 hypermethylated and 13 and 21 hypomethylated genes in differentiated papillary and follicular tumors, respectively. Interestingly, the other tumor types analyzed displayed more hypomethylated genes (280 in anaplastic and 393 in medullary tumors) than aberrantly hypermethylated genes (86 in anaplastic and 131 in medullary tumors). Among the genes indentified, we show that 4 potential tumor suppressor genes (ADAMTS8, HOXB4, ZIC1, and KISS1R) and 4 potential oncogenes (INSL4, DPPA2, TCL1B, and NOTCH4) are frequently regulated by aberrant methylation in primary thyroid tumors. In addition, we show that aberrant promoter hypomethylation-associated overexpression of MAP17 might promote tumor growth in thyroid cancer. CONCLUSIONS: Thyroid cancer subtypes present differential promoter methylation signatures, and nondifferentiated subtypes are characterized by aberrant promoter hypomethylation rather than hypermethylation. Additional studies are needed to determine the potential clinical interest of the tumor subtype-specific DNA methylation signatures described herein and the role of aberrant promoter hypomethylation in nondifferentiated thyroid tumors.

Neck schwannomas.

Schwannomas are peripheral nerve tumours of nerve sheath origin. Twenty-five to 45 percent of extracranial schwannomas occur in the head and neck region. We present 2 cases of schwannomas that arise from the vagus and cervical plexus. These lesions are uncommon and most often present as asymptomatic solitary neck mass. Preoperative diagnosis can be difficult and conservative surgical excision remains the treatment of choice, often requiring sacrifice of a portion of the nerve.

Prognostic significance of p53 expression in oral squamous cell carcinoma without neck node metastases.

BACKGROUND: Aberrations of the p53 gene and overexpression of its protein are widely recognized markers of malignancy including oral squamous cell carcinomas. This study was performed to evaluate the relationship of immunoexpression of p53 protein in series of 91 squamous cell carcinomas of the oral cavity with clinicopathologic parameters and to investigate whether p53 immunoexpression might influence the clinical outcome of the disease. METHODS: From a group of 287 consecutive patients, 91 surgically treated ones were randomly selected. P53 protein expression was investigated by means of immunohistochemistry. Clinical and histopathologic data were gathered, and the patient survival was analyzed. RESULTS: Of the oral carcinomas, 52.7% (n = 48) overexpressed p53, using a threshold of 10% stained cell nuclei. There was a negative correlation of p53 immunoexpression with a histologic grade of differentiation (r = -0.236, p =.06) but not with clinical variables. Overall survival rate was 59% at 5 years. In univariate analysis, tumor size, node status, and advanced clinical stage were significantly associated with shortened overall survival. In patients without neck node metastases, p53 showed a strong correlation with survival (p =.01). In multivariate analysis performed only on N0 patients, tumor extension and p53 immunoexpression were found to be the only independent prognostic parameters with relative risks of 1.9 and 4.3, respectively. CONCLUSIONS: A strong relationship was observed between p53 immunoexpression and poor prognosis in patients with oral squamous cell carcinomas without neck node metastases.