Tumor-infiltrating lymphocytes (TILs) have shown a promising prognostic value in many epithelial cancers. We sought to assess the prognostic value of TILs in a multicenter cohort of early oral tongue squamous cell carcinoma (OTSCC). The percentage of TILs was assessed on the surgical resection slides stained with hematoxylin and eosin. The assessment of TILs was performed in the stromal compartment and in the intraepithelial compartment (at the invasive front and at the center of the tumor). We followed the method that was described recently by the International Immuno-Oncology Biomarker Working Group for the assessment of TILs. A total of 308 cases from the 5 Finnish university hospitals and from A.C. Camargo Cancer Center, São Paulo, Brazil, were included. We found a promising prognostic value for stromal TILs at the invasive front in the multivariable analysis with a hazard ratio of 2.61 (95% confidence interval [CI], 1.77-3.83; P
A role for incisional biopsy in preoperative prognostication is increasingly being advocated in oral tongue squamous cell carcinomas (OTSCC). Biopsies at two locations were compared, and prognostic factors in biopsies and their corresponding resections were evaluated. A total of 138 OTSCC biopsy slides from Finland and Saudi Arabia were compared for size (horizontal and vertical) and invasive front. The Finnish cases were assessed for tumor stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs) using light microscopy and digital image analysis assessment and compared. Furthermore, TSR, TILs, and previously analyzed budding and depth of invasion (BD) score in biopsies were compared with their evaluation in the corresponding resections. Fifty-nine percent of Finnish and 42% of Saudi Arabian biopsies were = 5 mm deep, while 98% of Saudi Arabian and 76% of Finnish biopsies were = 5 mm wide. Assessment of invasion front was possible in 72% of Finnish in comparison with 40% of Saudi Arabian biopsies. There was 86.8% agreement between TSR and 75% agreement between TIL evaluation using light microscopy and digital assessment. Significant agreement was obtained on comparing the TSR (p = 0.04) and BD (p
Mobile tongue squamous cell carcinoma (MTSCC) is known for its strong propensity for regional metastasis and poor patient survival despite aggressive treatment, thus calling for new and reliable markers for predicting prognosis and guiding therapeutic management. Towards this end, three classes of markers were investigated: cancer-associated fibroblasts (CAFs; a-SMA positivity) as a representative of the tumor microenvironment, maspin (mammary serine protease inhibitor) as a tumor marker likely to be modulated by factors within the tumor microenvironment, and DNA content and Ki-67 labeling index as inbuilt tumor markers in 128 cases of MTSCC using immunohistochemistry and image cytometry. Of these markers, only CAF density was independently and relatively strongly associated with elevated mortality from MTSCC. The hazard ratio in the CAF-rich type of tumor microenvironment was 4.85 (95% CI 1.41-16.6, versus the CAF-poor) when adjusted by proportional hazards modeling for the center where the patient was managed, gender, tumor stage, presence of neck metastasis and age at diagnosis. CAF density was unrelated to non-MTSSC mortality. Given the strong association between increased CAF density and higher mortality in MTSCC, routine assessment of CAF density for disease course prognosis and inclusion as an integral part of treatment protocols are recommended.
Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy and its grading is greatly consequential in the management and prognosis of patients with the disease.
To compare histologic grading systems in MEC of minor salivary glands.
Two qualitative (modified Healy and Memorial Sloan-Kettering Cancer Center [MSKCC] methods) and two quantitative (Armed Forces Institute of Pathology [AFIP] and Brandwein methods) were evaluated.
Diagnostics slides of 19 patients including one recurrent case were evaluated using the four grading systems.
Percentages and proportions were used.
Agreement across all grading system was found to be very low (32%) while there was a better agreement between AFIP and MSKCC methods (84%) between modified Healy and Brandwein (58%). The method that gave the poorest agreement with all the others was the Brandwein grading. In general, the AFIP and MSKCC methods tended to grade the tumors lower while the Brandwein and modified Healy methods seemed to grade them higher.
Most MEC of minor salivary glands appear to be low-grade tumors. It is conceivable that some grading methods (Brandwein and modified Healy) may lead to an unnecessary escalation of management methods in these tumors. The MSKCC method may have emphasized some parameters which may not have much importance in minor salivary gland MEC. The AFIP method appears to be the most appropriate to use for the grading of minor salivary gland MEC. Further studies are required to confirm or disprove this finding.
Oral (mobile) tongue squamous cell carcinoma (SCC) is characterized by a highly variable prognosis in early-stage disease (T1/T2 N0M0). The ability to classify early oral tongue SCCs into low-risk and high-risk categories would represent a major advancement in their management.
Depth of invasion, tumor budding, histologic risk-assessment score (HRS), and cancer-associated fibroblast (CAF) density were studied in 233 cases of T1/T2 N0M0 oral tongue SCC managed in 5 university hospitals in Finland.
Tumor budding (=5 clusters at the invasive front of the tumor) and depth of invasion (=4 mm) were associated with poor prognosis in patients with early oral tongue SCC (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.17-3.55; HR, 2.55; 95% CI, 1.25-5.20, respectively) after multivariate analysis. The HRS and CAF density did not predict survival. However, high-risk worst pattern of invasion (WPOI), a component of HRS, was also an independent prognostic factor (HR, 4.47; 95% CI, 1.59-12.51).
Analyzing the depth of invasion, tumor budding, and/or WPOI in prognostication and treatment planning of T1/T2 N0M0 oral tongue SCC is recommended.
Salivary gland tumors (SGTs) of epithelial origin are relatively rare, and worldwide reports show considerable variations in their epidemiology. The aim of this study was to examine, for the first time, the records of SGTs from two very distant geographical locations, Finland (two medical centers) and Israel (one medical center) between 1999 and 2008, based exclusively on the 2005 WHO classification of head and neck tumors, and to compare those data to the other available (single-center) studies that used the same classification. A total of 2,218 benign and malignant tumors diagnosed in the three centers were analyzed. Differences in classification of the tumors were found between the two geographical locations as well as between the two centers from Finland. There was a higher ratio of benign-to-malignant SGTs in the Finnish centers (5.4:1 and 7:1) compared to the Israeli center (2:1), a higher frequency of tumors of minor salivary glands in the Israeli center (34%) than in the Finnish centers (4 and 11%), and a higher frequency of malignant SGTs in the minor salivary glands in Israel (64.5%) than in Finland (10.9 and 27%). The diversity of these multicenter data are compatible with reports from different parts of the world. We conclude that conducting epidemiologic surveys based on the latest WHO classification provides clinicopathologic correlations on SGTs that seem to be characteristic even in small geographical regions.
Cites: Exp Gerontol. 2000 Feb;35(1):85-9310705042
Cites: Am J Surg Pathol. 2011 Aug;35(8):1168-7621716087
Claudins (CLDNs) are a family of membrane proteins important for permeability of tight junctions. They have also been implicated in carcinogenesis and tumor progression. We analyzed patterns of distribution and intensity of expression of CLDNs 1, 3, 4, and 7 in mucoepidermoid carcinoma (MEC) of salivary gland in 39 patients. Correlations between the expression of CLDNs, tumor grade, and survival were explored. In immunohistochemical analysis, high expression of CLDN 1 was seen in low-grade MEC, and it appeared to be a suitable auxiliary marker of good prognosis. It classified MEC similarly to histological grading in 89.7% of cases (p?=?0.001). High CLDN 3 expression was seen in intermediate- and high-grade MEC, while it was low in low-grade MEC. CLDN 3 intensity correctly categorized tumors into grades in 71.8% of cases (p?=?0.017). However, in multivariate analysis CLDN 1 and CLDN 3 did not achieve significance over tumor grade in predicting patient behavior. We conclude that analysis of staining intensities of CLDN 1 and 3 is useful as an auxiliary diagnostic and prognostic tool in patients with salivary gland MEC.
The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed.
Oral (mobile) tongue squamous cell carcinoma (OTSCC) is the most common cancer diagnosed within the oral cavity. Due to the inherent disadvantages of the mobile tongue OTSCC behaves aggressively and is generally associated with higher rates of occult metastasis and neck nodal metastasis than any other cancer of the oral cavity. The prognosis remains relatively poor and is still heavily reliant on TNM (tumor, node, metastasis) staging of the tumor despite a vast array of literature on possible prognostic indicators. This is a two-part article which examines the methods by which the behavior and prognosis of OTSCC has been studied, the prognostics markers, and the relevance and future direction of prognostic studies. In this first part, we discuss the relative merits of the methods used in prognostic studies and the clinicopathologic prognostic factors.
Squamous cell carcinoma of the oral (mobile) tongue (OTSCC) is increasingly regarded as a biologically different entity compared to cancer affecting other oral sites. It is more aggressive and generally associated with a higher rate of metastasis. This is the concluding part of our two-part article that examines the methods by which the behavior and prognosis of OTSCC has been studied, the prognostics markers, and the relevance and future direction of prognostic studies. In this part, we continue our discussion of the histopathologic and molecular prognostic factors, and serum and salivary biomarkers in of OTSCC, and emphasize the need to regard OTSCC as a high risk variant of oral cancer. We conclude with future direction of prognostic studies of OTSCC.