PubMed Health⌕ Search

Biomedical subjects

J Klijanienko

Publications and source records attributed to J Klijanienko.

10 recordsLinked to original sources
PubMed2026

Multiregion profiling of genomic and transcriptional heterogeneity in head and neck squamous-cell carcinoma.

BACKGROUND: Intratumoral heterogeneity (ITH) is thought to contribute to tumour evolution and treatment resistance but its biological and clinical significance in localised head and neck squamous-cell carcinoma (HNSCC) remains incompletely understood. PATIENTS AND METHODS: In the prospective SCANDARE study, we analysed 87 patients with resectable HNSCC treated with upfront surgery. Two to five spatially distinct tumour regions per patient underwent pathological evaluation, targeted DNA sequencing, and bulk RNA sequencing. Genomic ITH (gITH) was quantified using clonal deconvolution and Shannon diversity indices, whereas transcriptional heterogeneity (tITH) was assessed using the intratumour expression distance metric. Associations between ITH, molecular features, tumour microenvironment composition, and clinical outcomes were explored using multivariable statistical models. RESULTS: Pathology-based spatial heterogeneity showed limited prognostic value. gITH was common, with 37% of tumours displaying regionally heterogeneous pathogenic variants, including spatially actionable alterations in 10% of patients. In an initial multivariable Cox model, higher gITH was associated with shorter disease-free survival. However, after Ridge-penalised modelling and bootstrap internal validation, the effect size was attenuated [corrected hazard ratio 1.42, 95% confidence interval (CI) 0.91-2.75]. The overall model retained moderate discriminative performance (optimism-corrected C-index 0.69, 95% CI 0.59-0.79). gITH was associated with tumour cellularity, reduced estimated endothelial cell infiltration, and alterations in KMT2C and PIK3CA. tITH differed according to human papillomavirus (HPV) status, with lower tITH in HPV-positive tumours, and was associated with distinct biological pathways and genomic alterations. Genomic and tITH were not correlated. CONCLUSIONS: This prospective multiregion study provides a comprehensive characterisation of genomic and tITH in localised HNSCC. Our findings highlight substantial spatial molecular diversity within primary tumours and suggest potential associations between heterogeneity, tumour biology, and clinical outcome that warrant validation in independent cohorts.

head and neck squamous-cell carcinoma (HNSCC)↗
PubMed1992

Quantitative mapping of 4'-iododeoxyrubicin in metastatic squamous cellcarcinoma by secondary ion mass spectrometry (SIMS) microscopy.

Secondary ion mass spectrometry microscopy enables quantitative mapping of chemical elements in tissue sections. It was used for the detection of 127I contained in 4'-iododeoxyrubicin (IDX). Metastatic cutaneous squamous cell carcinoma from 7 patients participating in a phase I study (IDX dose, 80 mg/m2, 10-min i.v. infusion) were biopsied 10 min after drug administration and compared to 3 controls who did not receive any treatment (one squamous cell carcinoma and 2 gastric carcinomas). Biopsy specimens were fixed and embedded in methacrylate resin. Then, serial semithin sections (3 microns) were analyzed simultaneously with ionic and optimal microscopes in order to identify the histological structures given by the 31P distribution in which 127I in IDX was mapped. The iodine signal was undetected in controls and found mainly in the nuclei of tumor cells of the treated patients. Its concentration, measured in at least 30 nuclei of each specimen, was undetectable in 8% of the nuclei and 91% of them were within 1 and 16 ng/mg. The mean concentration of each specimen ranged from 5 to 23 ng/mg. This study demonstrates the capacity of ion microscopy to localize a cytotoxic drug (IDX) in a human biopsy specimen without the need for radioactive labeling and enables the evaluation of drug penetration in cancer cells which is critical for its activity.

Carcinoma, Squamous Cell↗
PubMed1992

True carcinosarcoma of the larynx.

A case of carcinosarcoma of the larynx and pyriform sinus with sarcomatous and epithelial malignant components is described in a 68-year-old male. The primary site was composed of spindle-shaped malignant mesenchymal cells with osteosarcomatous and chondrosarcomatous differentiation intermingled with areas of well differentiated squamous cell carcinoma, tubular and papillary adenocarcinoma, and trabecular neuroendocrine carcinoma. The metastatic lymph node showed squamous cell carcinoma and chondrosarcoma. Immunohistochemical studies showed that keratin was present in epithelia cells and negative in sarcoma, whereas vimentin and S-100 protein were present in sarcoma, but negative in carcinoma. Neuron-specific enolase was present in the neuroendocrine part of the tumour.

Aged↗
PubMed1990

Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas.

The c-Ha-ras gene was analysed by Southern blot hybridisation in 67 specimens of lymph node metastases and in 25 specimens of primary tumours obtained from 85 untreated patients with head and neck squamous cell carcinoma. The loss of one c-Ha-ras allele was observed in 10/46 (22%) tumours from heterozygous patients for this locus. Different genes, located as the c-Ha-ras gene on the short arm of chromosome 11, were also found to be deleted suggesting that the deletion of other genes could play a role in aggressiveness of head and neck carcinomas. Using polymerase chain reaction, mutation at codon 12 was detected in only 2/54 (3.8%) tumours but no mutation involving codon 61 was found. Neither gene amplification nor gene rearrangement could be observed. Total RNA was prepared from 79 of these tumour specimens and analysed by Northern and slot blot hybridisation. A 1.2 kb c-Ha-ras transcript band was detected in all the RNA preparations. Relatively high c-Ha-ras transcript levels were found in 18% of lymph node metastases and in 21% of primary tumours, indicating no significant differences between these cancers. Moreover, the c-Ha-ras mRNA levels were not significantly greater in the primary tumours than in the normal mucosae in 10/12 cases for which both tissues were analysed. These data indicate that c-Ha-ras gene does not seem to be strongly involved in head and neck carcinomas at that advanced stage of the disease, as this was previously reported for earlier clinical stages.

Blotting, Northern↗
PubMed1990

So-called branchiogenic carcinoma is actually cystic metastases in the neck from a tonsillar primary.

In 1974, we reported on six patients with squamous cell carcinoma arising in the tonsillar area who presented with a characteristic form of cystic nodal metastasis. This study reports on an additional 21 patients with this entity. Treatment of these patients included removal of the cystic metastasis with or without radical neck dissection and irradiation of Waldeyer's ring. Two patients have died of unrelated disease and two were lost to follow-up, but the remainder are alive without disease 2 months to 12 years following initial diagnosis. We believe that cystic metastases from tonsillar squamous cell carcinomas have often been mistaken for either primary squamous cell carcinomas of branchiogenic origin or with branchial cleft cysts. The distinctive histological features of cystic metastases reviewed after its correct identification can lead to the discovery of an unsuspected primary lesion and result in specific treatment options.

Adult↗
PubMed1989

Undifferentiated carcinoma of nasopharyngeal type of tonsil.

A review of 2262 squamous cell carcinomas of the tonsillar region seen at the Institut Gustave-Roussy, Villejuif, France, from 1970 to 1986 showed 1837 well- and poorly differentiated squamous cell carcinomas and 425 undifferentiated squamous cell carcinomas. Eighteen patients with undifferentiated squamous cell carcinomas presented histologic characteristics of undifferentiated carcinomas of nasopharyngeal type. Radiosensibility and radiocurability (complete sterilization with 70 Gy administered) was found in this group with an excellent long-term control of local disease (77% at 10 years actuarial). Epstein-Barr virus-related serologic tests were performed for seven patients. Four of them presented the serologic anti-Epstein-Barr virus titer patterns, generally associated with undifferentiated carcinomas of nasopharyngeal type (1280 to 5120 for viral capsid antigen/IgG and 40 to 320 for viral capsid antigen/IgA). These observations confirm that undifferentiated carcinomas of the nasopharyngeal type may arise outside the nasopharynx.

Adult↗
PubMed1989

Significance of keratin 13 and 6 expression in normal, dysplasic and malignant squamous epithelium of pyriform fossa.

It has been suggested that cytokeratin 13 is a useful marker of malignancy. We examined normal squamous cell epithelia, hyperplasia, dysplasias of various grades, intraepithelial neoplasia and invasive squamous cell carcinomas of the pyriform fossa using K13 and KL1. Positive staining for K13 was seen in all normal or hyperplastic benign epithelia, was inconstant in dysplasia, and intraepithelial neoplasia and carcinoma was negative. KL1 expression is constant and non significant. These results suggest that tumour cells are unable to synthesize keratin 13 a finding which may be valuable in surgical pathology.

Biomarkers, Tumor↗
PubMed1989

Clear cell carcinoma arising in pleomorphic adenoma of the minor salivary gland.

Malignant change arising in pleomorphic adenoma of the salivary glands is uncommon, with a reported incidence of 2-10 per cent. Only one case where a pleomorphic adenoma became a clear cell carcinoma appears to have been published in the English literature. An additional case of clear cell carcinoma arising in pleomorphic adenoma of a minor salivary gland is reported and the relevant literature discussed.

Adenocarcinoma↗