Anita M. Borges

Elective versus therapeutic neck dissection in early carcinoma of the oral tongue

A prospective, randomized trial was carried out to assess the value of elective versus therapeutic neck dissection in early squamous cell carcinoma of the oral tongue. Disease-free survival (median follow-up 20 months) was 52 percent versus 63 percent in patients who underwent hemiglossectomy alone and those who underwent hemiglossectomy and radical neck dissection, respectively (difference not statistically significant). Patients with a tumor depth of less than 4 mm did significantly better than those with a tumor depth of greater than 4 mm; they were also more likely to have uninvolved nodes at elective radical neck dissection compared with those with a tumor depth of greater than 4 mm. However, when the survival rates of patients in the two treatment groups were compared with respect to a tumor depth of 4 mm, there was no significant difference between the hemiglossectomy and the hemiglossectomy and radical neck dissection groups. A policy of interval elective radical neck dissection only in those with a tumor depth of greater than 4 mm may optimize cure rates and avoid neck dissection in those unlikely to develop neck recurrence.

Osteosarcoma of the craniofacial bones: A Clinico-Pathological study

Thirty-four cases of osteosarcoma involving the craniofacial bones over a period of 19 years were reviewed. They formed 6.2% of osteosarcomas occurring in the skeleton during the same period at the Tata Memorial Hospital. Mean age of occurrence was 30.9% years, with a range of 7 to 61 years. Male preponderance was noted in maxillary tumours (M:F = 2.6:1), while the mandibular tumours occurred with equal frequency in both sexes. The mandible was the bone of origin in 56%, maxilla in 32% and other craniofacial bones in 12% of patients. Histological sub-type did not affect the prognosis. Radical surgery with resection of adequate disease-free margins is the most effective mode of treatment. Morbidity and mortality is due to extensive local recurrence of disease, particularly with maxillary tumours. Metastasis to other organs occurs rarely. No statistically significant difference in survival was observed between tumours of the mandible and maxilla, or between patients above and below 20 years of age.

p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India

The inactivation of p53 tumour suppressor gene vis-á-vis point mutation, overexpression and degradation due to Human Papilloma virus (HPV) 16/18 infection, was examined in chewing tobacco-associated oral cancers and oral leukoplakias from India. The analysis of mutations was assessed by polymerase chain reaction (PCR) with single strand conformation polymorphism (PCR-SSCP) of exons 5-9 on DNA from 83 oral cancer cases, and the mutations confirmed by direct nucleotide sequencing of the PCR products. p53 protein expression was evaluated by immunohistochemical analysis on paraffin-embedded sections of 62 representative oral cancer biopsies and 22 leukoplakias, using p53-specific monoclonal antibody DO-7. The presence of HPV16/18 was detected in the 83 oral cancer cases by PCR analysis using HPV L1 consensus sequences, followed by Southern hybridization with type-specific oligonucleotide probes. Forty-six per cent (38/83) of oral cancer tumours showed p53 alterations, with 17% (14/83) showing point mutations, 37% (23/62) with overexpression and 25% (21/83) with presence of HPV16 wherein the E6 HPV16 protein degrades p53. HPV18 was not detected in any of the samples. Ninety-two per cent concordance was observed between missense point mutations and overexpression of p53 protein. A significant correlation was not observed between p53 alterations in oral cancer and clinico-pathological profile of the patients. Twenty-seven per cent (6/22) of oral leukoplakias showed p53 overexpression. The overall p53 alterations in oral cancer tissues and oral lesions are comparable to data from the oral cancers reported in the Western countries with smoking and alcohol-associated oral cancers, and suggest a critical role for p53 gene in a significant proportion of oral cancers from India. The overexpression of p53 protein in leukoplakias may serve as a valuable biomarker for identifying individuals at high risk of transformation to malignant phenotype.

Cytokeratin expression in squamous cell carcinomas of the tongue and alveolar mucosa

Cytokeratins (CK), the intermediate filament markers for epithelial cells were analysed in 23 squamous cell carcinomas (SCC) of the tongue and 11 SCC of the alveolar mucosa (AM) by SDS-PAGE, immunoblotting and two dimensional gel electrophoresis. Normal human adult ventral tongue expresses CK nos 4, 5, 6, 13, 14, 16 (17) while the dorsal tongue expresses CK nos 1, 5, 6, 10, 14, 16 (17). CK 5 and CK 14 were not detected in a majority of samples and CK 18, a marker of simple epithelia, was aberrantly expressed in 18 samples. Normal human adult AM expresses CK nos 4, 5, 6, 13, 14, 16 (17). Among 11 SCC of AM, CK 4 and CK 5 were detected in only two samples each. CK 1 and CK 10 were aberrantly expressed in nine and one samples, respectively. The basic CKs such as CK 4, 5 and 14 were not expressed in SCC at both these sites while others like CK 1 and 18 were aberrantly expressed. Thus, non-expression of basic keratin, CK 5, of the oral lining epithelia and aberrant expression of simple epithelial keratins seem to be the major events in malignant transformation in the oral epithelia.

Genomic Profiling of Advanced-Stage Oral Cancers Reveals Chromosome 11q Alterations as Markers of Poor Clinical Outcome

Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1–q22.2 and losses of 17p13.3 and 11q23–q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers.

Teratocarcinosarcoma of the paranasal sinuses: a clinicopathologic and immunohistochemical study.

We report four cases of sinonasal teratocarcinosarcoma (SNTCS), a rare malignant tumor that displays combined features of an immature or malignant teratoma and a carcinosarcoma. The patients, three men and one woman, were all adults ranging in age from 21 to 69 years who presented with nasal obstruction and epistaxis. The tumors were typically composed of round cells and short spindle cells with neuroectodermal/rosette-like structures. Also seen were foci of fetal-like squamous epithelium, glandular epithelium, immature mesenchyme, immature cartilage, and neuronal differentiation. Immunohistochemistry performed in three cases showed expression of vimentin, CD99 (MIC2), and neuron-specific enolase in most cells, and focal expression of cytokeratin, epithelial membrane antigen, alpha fetoprotein, glial fibrillary acidic protein, chromogranin, and synaptophysin. The tumors were consistently negative for beta human chorionic gonadotrophin, neurofilament protein, and leukocyte common antigen. The entities considered in the differential diagnosis were poorly differentiated carcinomas, sarcomas, and olfactory neuroblastoma. We suggest that these neoplasms arise from a primitive cell capable of organized divergent differentiation.

Histologic trends in thyroid cancer 1969-1993: a clinico-pathologic analysis of the relative proportion of anaplastic carcinoma of the thyroid.

It was observed that new presentations of anaplastic carcinoma of the thyroid had become infrequent in the last two decades.

Angiogenesis is redundant for tumour growth in lymph node metastases

Angiogenesis is redundant for tumour growth in lymph node metastases

Understanding the role of keratins 8 and 18 in neoplastic potential of breast cancer derived cell lines.

Background Breast cancer is a complex disease which cannot be defined merely by clinical parameters like lymph node involvement and histological grade, or by routinely used biomarkers like estrogen receptor (ER), progesterone receptor (PGR) and epidermal growth factor receptor 2 (HER2) in diagnosis and prognosis. Breast cancer originates from the epithelial cells. Keratins (K) are cytoplasmic intermediate filament proteins of epithelial cells and changes in the expression pattern of keratins have been seen during malignant transformation in the breast. Expression of the K8/18 pair is seen in the luminal cells of the breast epithelium, and its role in prognostication of breast cancer is not well understood. Methodology/Principal Findings In this study, we have modulated K8 expression to understand the role of the K8/18 pair in three different breast epithelium derived cell lines: non-transformed MCF10A, transformed but poorly invasive MDA MB 468 and highly invasive MDA MB 435. The up-regulation of K8 in the invasive MDA MB 435 cell line resulted in a significant decrease in proliferation, motility, in-vitro invasion, tumor volume and lung metastasis. The down-regulation of K8 in MDA MB 468 resulted in a significant increase in transformation potential, motility and invasion in-vitro, while MCF10A did not show any changes in cell transformation assays. Conclusions/Significance These results indicate the role of K8/18 in modulating invasion in breast cancer -its presence correlating with less invasive phenotype and absence correlating with highly invasive, dedifferentiated phenotype. These data may have important implications for prognostication of breast cancer.

Lateral thyrotomy for neurilemmoma of the larynx

We present a rare case of neurilemmoma of the larynx, which was excised through a lateral thyrotomy approach with resulting restoration of laryngeal function. The advantage of the lateral thyrotomy approach for submucous tumours of the larynx is discussed.