Related Squamous Cell Carcinoma Research Articles

Adiposity and risk of oesophageal cancer subtypes in the Million Women Study.

The strong association of body mass index (BMI) with increased oesophageal adenocarcinoma risk is established, but its relationship with oesophageal squamous cell carcinoma is less clear. There is little evidence regarding the association of abdominal adiposity with either subtype. In a large prospective cohort of women in the UK, mean age 56.2 [standard deviation (SD) = 4.9] years, we investigated the risk of oesophageal adenocarcinoma and squamous cell carcinoma in relation to self-reported BMI, waist circumference (WC) and waist-hip ratio (WHR), using Cox regression to estimate adjusted relative risks (RR) and 95% confidence intervals (CIs), taking account of potential reverse causation bias. During mean follow-up of 17.7 (SD = 4.9) years, 1386 adenocarcinomas and 1799 squamous cell carcinomas of the oesophagus were registered among 1 255 529 women. Compared with women of BMI 22.5 to <25 kg/m2, those with BMI ≥35 kg/m2 had a 2.5-fold risk of adenocarcinoma (adjusted RR = 2.46, 95% CI = 1.99-3.05) and an almost 70% reduction in risk of squamous cell carcinoma (RR = 0.32, 95% CI = 0.22-0.46). These associations were broadly similar in each 5-year follow-up period, and were evident in both never and ever smokers, although somewhat stronger for squamous cell carcinoma among current and past smokers than in never smokers (Pheterogeneity = 0.007). After controlling for BMI, WC and WHR were associated with risk of squamous cell carcinoma but not adenocarcinoma. In this population of middle-aged women, there was robust evidence that greater BMI is associated with an increased risk of oesophageal adenocarcinoma and a reduced risk of squamous cell carcinoma.

LncRNA GHET1 and LncRNA ZXF2 as New Biomarkers in Oral Squamous Cell Carcinoma in Relation to Clinicopathological Variables

Background: The utilization of molecular techniques in detecting cancer has resulted in an improved prediction of outcomes. Oral squamous cell carcinoma (OSCC) is a prevalent illness that is frequently detected in its late stages. Therefore, finding molecular biomarkers that lead to the early detection of OSCC is of great importance. Objectives: This study aimed at evaluating the expression levels of long non-coding RNA (LncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) and lncRNA ZXF2 in OSCC patients and their relationship with clinical pathology variables due to biomarker discovery and early diagnosis of OSCC. Methods: Tissue sampling was performed after selecting 30 OSCC patients and 30 healthy individuals from Emam-Khomeini Hospital, Tehran, Iran. Then, RNA extraction and cDNA synthesis were performed from these samples, using the relevant kits and their quantity and quality were measured, using nanodrop and agarose gel electrophoresis, respectively. For molecular biomarker identification and validation, real-time PCR (RT-PCR) was utilized to assess the expression of lncRNA GHET1 and lncRNA ZXF2. Data analysis was done, using GraphPad prism V.8 software. Results: The results showed that the expressions of both lncRNA GHET1 and lncRNA ZXF2 in OSCC tumor tissue increased compared to normal tissue (P &lt; 0.0001). Receiver operating characteristic (ROC) analysis indicated that lncRNA GHET1 and lncRNA ZXF2 have the capability to be employed as biomarkers for OSCC detection. However, no significant relationship was observed between lncRNA GHET1 and lncRNA ZXF2 expressions with clinicopathological variables such as tumor stage and grade as well as patients' age. Conclusions: LncRNA GHET1 and lncRNA ZXF2 have the potential to be used as biomarkers in the early detection of OSCC and evaluating their expression in clinical settings are recommended. The use of these biomarkers in the early detection of OSCC can prevent the high mortality rate of OSCC patients. In the current study, the important role of the studied lncRNAs in OSCC diagnosis was shown. However, further studies are needed to confirm this.

Prognostic Significance of Worst Pattern of Invasion in oral cavity Squamous Cell Carcinoma in relation to lymph node metastasis —A Retrospective Study from tertiary care centre

Prognostic Significance of Worst Pattern of Invasion in oral cavity Squamous Cell Carcinoma in relation to lymph node metastasis —A Retrospective Study from tertiary care centre

Comparison between Anneroth’s Broder’s Grading Systems in Oral Squamous Cell Carcinoma in Relation to Histopathological Prognostic Factors

Background: Oral squamous cell carcinoma (OSCC) is a commonly occurring head and neck cancer. It has a high prevalence, and is associated with a high mortality rate. OSCC occurs due to many etiological factors, but smoking and alcohol remain the most common risk factors. The histological grading of tumors has been used to predict the clinical behaviour of OSCC. Broder’s initiated quantitative grading in cancer. Anneroth’s and Hansen developed another grading system for grading of OSCC’s. With this background, a study was undertaken to compare between Anneroth’s Broder’s grading systems in oral squamous cell carcinoma in relation to histopathological prognostic factors. Material Methods: A retrospective study was carried out on 50 formalin fixed paraffin embedded tissue blocks of the confirmed cases of Oral squamous cell carcinoma in the archives of department of oral pathology, Govt. Dental College Hospital, Srinagar. The cases were evaluated on the basis of Broder’s Anneroth’s grading systems for OSCC the comparison of the systems was made pertaining to histopathological prognostic parameters. Results: In our study according to Anneroth’s system maximum cases comes under grade III while in Broder’s system maximum cases are in grade I II. Conclusion: Anneroth’s classification provides us a detailed analysis of grading the cases according to scoring of each parameter. Thus, it is more informative than Broder’s grading system.

Incidence and epidemiology of conjunctival squamous cell carcinoma in relation to the HIV epidemic in South Africa: a 25-year analysis of the National Cancer Registry (1994–2018)

AimsTo describe the incidence and epidemiology of conjunctival squamous cell carcinoma (CSCC) in South Africa over a 25-year period (1994–2018), with particular reference to the HIV epidemic.MethodsIncident cases of histologically...

Prognostic Value of Lymph Node Yield, Lymph Node Density, and pN in Oral Cancer.

To investigate thresholds for lymph node yield (LNY), lymph node density (LND), and pN in patients with oral squamous cell carcinoma in relation to previous findings in the literature. Retrospective register-based study. Copenhagen Oral Cavity Squamous Cell Carcinoma database. Appropriate thresholds for LNY, LND, and pN were determined by areas under the curve and subsequently subjected to multivariate analysis. Five-year overall survival and 3-year recurrence-free survival were determined by Kaplan-Meier survival curves. In total, 413 patients diagnosed with oral squamous cell carcinoma were included. In the pN0 cohort, no superior/prognostic LNY cutoff values were detected. In the pN+ cohort, areas under the curve determined thresholds of LNY, LND, and pN to be 21 nodes, 5%, and 3 metastases, respectively. The 5-year overall survival was 52% for patients with LNY ≥21 vs 38% for patients with LNY <21 (hazard ratio [HR], 1.49; 95% CI, 1.05-2.11; P < .05), 60% for patients with LND ≤5% vs 38% for patients with LND >6% (HR, 1.63; 95% CI, 1.03-2.57; P < .05), and 43% for patients with pN <3 vs 26% for patients with pN ≥3 (HR, 1.40; 95% CI, 1.04-2.15; P < .05). Increased nodal yield, decreased LND, and decreasing number of pN were associated with significantly improved survival outcomes. LNY might serve as a prognosticator of survival as well as a surgical quality indicator. LND may have implications as a tool in cancer staging and treatment planning.

Long-Term Survival and Recurrence in Oropharyngeal Squamous Cell Carcinoma in Relation to Subsites, HPV, and p16-Status.

Simple SummaryLong-term survival in patients with oropharyngeal cancer is sparsely studied, but atypical recurrences in human papillomavirus-positive (HPV+) oropharyngeal cancer have been indicated. Furthermore, while the role of HPV is well established in tonsillar and base of tongue cancer, the dominant oropharyngeal subsites, its role in the minor oropharyngeal sites (the oropharyngeal walls, the uvula, and the soft palate) is not fully elucidated. The aim of this retrospective study was therefore to assess long-term outcome in relation to oropharyngeal sub-sites and HPV/p16 status. We confirm the prognostic role of p16+ in tonsillar and base of tongue cancer, but not the other sites. We find that combined HPV/p16-status gives better prognostic information than p16 alone. Lastly, we show that p16− cancer has more locoregional and late recurrences compared to p16+ cancer. Consequently, only combined HPV/p16 positivity in patients with tonsillar and tongue base cancer should be used in future treatment de-escalation trials.Long-term survival data in relation to sub-sites, human papillomavirus (HPV), and p16INK4a (p16) for patients with oropharyngeal squamous cell carcinoma (OPSCC) is still sparse. Furthermore, reports have indicated atypical and late recurrences for patients with HPV and p16 positive OPSCC. Therefore, we assessed long-term survival and recurrence in relation to oropharyngeal subsite and HPV/p16 status. A total of 529 patients with OPSCC, diagnosed in the period 2000–2010, with known HPVDNA and p16-status, were included. HPV/p16 status and sub-sites were correlated to disease-free and overall survival (DFS and OS respectively). The overexpression of p16 (p16+) is associated with significantly better long-term OS and DFS in tonsillar and base of tongue carcinomas (TSCC/BOTSCC), but not in patients with other OPSCC. Patients with HPVDNA+/p16+ TSCC/BOTSCC presented better OS and DFS compared to those with HPVDNA−/p16− tumors, while those with HPVDNA−/p16+ cancer had an intermediate survival. Late recurrences were rare, and significantly more frequent in patients with p16− tumors, while the prognosis after relapse was poor independent of HPVDNA+/−/p16+/− status. In conclusion, patients with p16+ OPSCC do not have more late recurrences than p16−, and a clear prognostic value of p16+ was only observed in TSCC/BOTSCC. Finally, the combination of HPVDNA and p16 provided superior prognostic information compared to p16 alone in TSCC/BOTSCC.

Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume

BackgroundLocoregional recurrence remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC). Human papilloma virus (HPV)-associated HNSCCs generally have a good prognosis but may recur even after standard photon radiotherapy (RT). Another incentive in observing patterns of recurrence is increased use of highly conformal techniques such as proton therapy. We therefore studied geographic distribution of recurrent tumors in relation to the high-risk treatment volume in a cohort of patients with HNSCC receiving combined modality therapy. MethodsMedical records of 508 patients diagnosed with HNSCC in 2010–2015 were reviewed. We identified a subgroup that had local and/or regional recurrence at hybrid positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI). We adapted p16 as a surrogate marker for HPV-positivity and only patients with known p16 status were eligible for a detailed analysis where recurrent tumor was copied on the planning CT and the dose received by the recurrent tumor volume was determined using dose-volume histograms. ResultsTwenty-five patients who had received either cisplatin (n = 23) or cetuximab-enhanced (n = 2) RT were identified. 31 locoregional recurrent tumors were detected among 18 p16 negative and 7 p16 positive patients. Of recurrent tumors 14 (45%) were classified as in-field, 5 (16%) as marginal miss, and 12 (39%) as true miss. p16 positive patients had 4 in-field, 2 marginal, and 1 true miss. By contrast, p16 negative patients had 10 in-field, 3 marginal, and 11 true miss recurrences. ConclusionsBoth p16 positive and negative HNSCC recur in high-risk treatment volume despite the common view of high radiosensitivity of the former. Biomarkers predicting radioresistance should be characterized in p16 positive tumors before widely embarking on de-escalated CRT protocols. Another concern is how to decrease the number of true or marginal misses in p16 negative cases despite multimodality imaging-based target delineation.

Oral Squamous Cell Carcinoma in Relation with Depth of Invasion and Lymph Node Metastasis

Background: Squamous cell carcinoma of oral cavity has become one of the most common malignancies in Nepal. Neck node involvement is frequently seen in this type of malignancy. Depth of invasion is one of the most important criteria for determining further management of the patient. This study is undertaken to see whether the depth of tumor invasion is a reliable parameter for predicting regional lymph node metastasis.&#x0D; Methods: This retrospective study was done among 85 patients of pathology department of the College of Medical Sciences Teaching Hospital, Bharatpur from May to Oct 2019. &#x0D; Results: This study found that most of the cases of oral squamous cell carcinoma had occurred in old age within 60-70 years of age. The most common site of occurrence for oral squamous cell carcinoma was tongue (60%), followed by lower alveolus (20%). The depth of invasion of 5mm and more was among 89% of the cases while cervical lymph node metastasis was among 53% cases. Most of the cases (60%) were well-differentiated (Grade I). There was no statistical relationship between depth of invasion and lymph node metastasis (p&gt;0.05).&#x0D; Conclusions: The most common site of oral squamous cell carcinoma was tongue. Depth of invasion was not a predictor for lymph node metastasis.&#x0D; Keywords: depth of invasion; lymph node metastasis; oral squamous cell carcinoma; simple compass divider.

Dermoscopic criteria of squamous cell carcinoma in relation to clinical variant and histopathologic differentiation grade

Background Although the dermoscopic criteria of squamous cell carcinoma (SCC) have been formerly described, little is known about the variance of those criteria according to the SCC clinical and histopathologic features. Objective To analyze the dermoscopic criteria of SCC and relate those criteria to the clinical variant and the histopathologic differentiation grade. Patients and methods This study included 16 patients with 17 lesions confirmed by histopathologic examination as invasive SCC. Patients’ demographics and clinical characteristics of lesions were reported. The dermoscopic criteria were studied and were related to the clinical variant and the histopathologic differentiation grade. Results Keratin and scales were more observed in well-differentiated SCC especially nodular and noduloulcerative lesions with diffuse and central distribution. Alternatively, ulceration and hemorrhage were detected more in moderately differentiated lesions especially noduloulcerative and ulcerative lesions. Well-differentiated lesions showed mainly linear, irregular vessels, while moderately differentiated lesions showed equally linear irregular vessels and coiled vessels. Nodular lesions showed mainly coiled vessels, while noduloulcerative and ulcerative lesions showed predominantly linear irregular vessels. White clues were more observed in well-differentiated lesions, with a predominant white to yellow background, and in nodular lesions. White to yellow color predominated in noduloulcerative lesions while combined color predominated in ulcerative lesions and in moderately differentiated lesions. Conclusion Dermoscopic criteria differ among the clinical SCC variants reflecting different histopathologic differentiation grades that could be linked to the clinical variant.

Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy.

ObjectivesAmbiguous results have been reported on the predictive value of the Ki‐67 proliferation index (Ki‐67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early‐stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut‐off values are attributing factors. Our aim was to elucidate the predictive value of the Ki‐67 PI for LC and disease‐specific survival (DSS) using a well‐defined series of T1‐T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA).MethodsA consecutive and well‐defined cohort of 208 patients with T1‐T2 LSCC treated with primary RT was selected. The Ki‐67 PI was determined using DIA. Mann‐Whitney U‐tests, logistic and Cox regression analyses were performed to assess associations between Ki‐67 PI, clinicopathological variables, LC and DSS.ResultsIn multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06‐4.59, P = .04) and alcohol use (HR 2.84, 95% CI 1.20‐6.71; P = .02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16‐8.64; P = .03). Ki‐67 PI was not associated with LC (HR 1.59; 95% CI 0.89‐2.81; P = .11) or DSS (HR 0.98; 95% CI 0.57‐1.66; P = .97). In addition, continuous Ki‐67 PI was not associated with LC (HR 2.03; 95% CI 0.37‐11.14, P = .42) or DSS (HR 0.62; 95% CI 0.05‐8.28; P = .72).ConclusionThe Ki‐67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment‐related decision‐making for LSCC.

A Comparative Study between Broders and Brynes Grading System of Oral Squamous Cell Carcinoma in Relation to Histopathological Prognostic Factors

A Comparative Study between Broders and Brynes Grading System of Oral Squamous Cell Carcinoma in Relation to Histopathological Prognostic Factors

Perineural Invasion in Oral Squamous Cell Carcinoma in Relation to Tumor Depth

Background: The American Joint committee on Cancer in their 8th edition staging manual regarded perineural invasion as one of the most important prognostic factors for Lip and Oral Cavity Squamous Cell Carcinoma, it also incorporated tumor depth of invasion in defining tumor size category in the new staging system. This study was conducted to evaluate the frequency of perineural invasion in oral squamous cell carcinoma and the effect of approaching tumor depth in this process. Materials and Methods: fifty-four formalin fixed paraffin embedded tissue blocks of radical resections of Oral Squamous Cell Carcinoma were cut and stained with Hematoxylin and Eosin stain, then evaluated for perineural invasion, with estimation of tumor depth of invasion for each case. Results: Perineural invasion was found in twenty-two cases of the study sample. The diameter of the largest nerve bundle that showed perineural invasion was found to have a positive significant correlation with tumor depth of invasion (p=0.025). Perineural invasion status in terms of (present, absent) showed a significant difference with patients’ age (p=0.037), also showed a significant association with tumor site (p=0.004), however, this association was non-significant in regard to tumor grade and stage (p=0.848, p=0.520) respectively. Conclusion: The attacking potential of preceding tumor depth and those cancers affecting young individuals may be reflected by the presence of neural infiltration by tumor cells. Tongue resected tumors should be carefully inspected for this deceptive biological process.

Margin status revisited in vulvar squamous cell carcinoma

ObjectiveTo determine the incidence of local recurrence of vulvar squamous cell carcinoma in relation to tumor- and/or precursor lesion free pathologic margins. MethodsConsecutive patients with primary vulvar squamous cell carcinoma surgically treated in two Dutch expert centers between 2000 and 2010 were included. All pathology slides were independently reviewed by two expert gynecopathologists, and local recurrence was defined as any recurrent disease located on the vulva. Time to first local recurrence was compared for different subgroups using univariable and multivariable Cox-regression analyses. ResultsIn total 287 patients with a median follow-up of 80months (range 0–204) were analyzed. The actuarial local recurrence rate ten years after treatment was 42.5%. Pathologic tumor free margin distance did not influence the risk on local recurrence (HR 1.03 (95% CI 0.99–1.06)), neither using a cutoff of eight, five, or three millimeters. Multivariable analyses showed a higher local recurrence rate in patients with dVIN and LS in the margin (HR 2.76 (95% CI 1.62–4.71)), in patients with dVIN in the margin (HR 2.14 (95% CI 1.11–4.12)), and a FIGO stage II or higher (HR 1.62 (95% CI 1.05–2.48)). ConclusionsLocal recurrences frequently occur in patients with primary vulvar carcinoma and are associated with dVIN (with or without LS) in the pathologic margin rather than any tumor free margin distance. Our results should lead to increased awareness among physicians of an ongoing risk for local recurrence and need for life-long follow-up. Intensified follow-up and treatment protocols for patients with dVIN in the margin should be evaluated in future research.

Immune Modulation in HLA-G Expressing Head and Neck Squamous Cell Carcinoma in Relation to Human Papilloma Virus Positivity: A Study From Northeast India.

Background: Tumor specific ectopic expression of the immunomodulatory molecule, HLA-G is known to mediate immune tolerance and promote carcinogenesis. Viruses too employ strategies to evade immune surveillance. Considering the role of both HLA-G and HPV in tumor growth and progression, it is pertinent to investigate the relationship between HLA-G and HPV in context of immune modulation in HNSCC.Method: A hospital based case–control study was conducted in histopathologically confirmed HNSCC tissues. HLA-G isoform expression and HPV association studies were carried out and mRNA levels of HLA-G, markers of proliferation and differentiation (ki-67, keratin 18, cyclin D1), immune checkpoint molecules (IL-10, PD-1. TGF-β), SOCS (SOCS1 and SOCS3) and pro-inflammatory cytokine IFN-γ were determined.Results: Higher expression of HLA-G was noted in HPV positive tumors (5.14 fold, p = 0.002). HLA-G7 was the most frequent isoform (29/80) found in HNSCC particularly in HPV positive tumors (13/16). In HPV negative tumors, all the checkpoint molecules were upregulated along with pro–inflammatory IFN-γ. In contrast, in HPV positive tumors, IFN-γ expression was higher (2.12 fold) but levels of IL-10, PD-1, TGF-β, SOCS1 and SOCS3 were markedly lower (fold change of IL-10 = 0.37, PD1 = 0.41, TGF-β = 0.17, SOCS1 = 0.055, SOCS3 = 0.027). HPV positive tumors were more proliferative and differentiated with higher expression of ki-67 and keratin18 (6.25 fold, p = 0.079 and 10.62 fold, p = 0.009). Decreased expression of cyclin D1 was noted in HPV positive tumors (6.94 fold, p = 0.006) than HPV negative tumors (17.69 fold). Also, HLA-G7 expressing HPV positive tumors showed lowest expression of cyclin D1. Interestingly, SOCS showed normal expression in HLA-G7 expressing HPV negative tumors (1.2 and 1.4 fold). IFN-γ was downregulated in HPV positive tumors without HLA-G7 (0.31 fold).Conclusion: Our data suggests that SOCS were downregulated irrespective of HLA-G positivity and IFN- γ expression appeared to be mediated by HLA-G. SOCS are reported to have anti-tumor activity and also SOCS and soluble HLA-G are known to interfere with cell cycle progression. Hence, through regulating HLA-G expression, HPV positive tumors could mediate immune suppression by manipulating SOCS, IFN-γ, IL-10 and cyclin D1 pathways which needs further exploration.

Assessment of Density of Neovascularization in Lower Lip Squamous Cell Carcinoma in Relation To Neoplasm Differentiation Grade in Patients with and without Neck Lymph Nodes Metastasis.

BACKGROUND:Squamous cell carcinoma (SCC) of the lower lip is a relatively rare carcinoma, with the incidence of 1 to 2%, but it is the most common carcinoma in the oral cavity accounting for 25-30% of all malignant oral tumours.AIM:This study aimed to determine the role of neovascularisation in the process of tumour progression.METHODS:We analysed the surgical specimens obtained from 60 patients with squamous cell carcinoma (SCC) of the lower lip. The examined group consisted of 45 specimens of patients without metastasis and 15 specimens of patients with metastasis in the regional lymph nodes. Histopathological slides were immunohistochemically stained with an antibody against CD34 and by hematoxylin & eosin staining for routine histopathological examination.RESULTS:The results obtained showed a statistically significant difference in the density of neovascularisation between groups of the SCC with different grade of differentiation (Kruskal-Wallis test: H (2, N = 60) = 30.0943, p = 0.00001). Statistical analysis also showed a significant difference in the density of vascularisation of lower lip SCC between patients without metastasis and patients with neck metastasis (Mann-Whitney U test, p = 0.000198). Applying Pearson’s chi-square test, we found a highly significant statistical difference in grade of SCC differentiation in patients with and without neck metastasis (p = 0.0000).CONCLUSION:In conclusion, the density of neoangiogenesis is increased in tumours with poorer differentiation and in patients with neck metastasis. So, the density of neovascularisation of the primary lip SCC may predict the tumour progression.

The Significance of Vimentinand Matrix Metalloproteinase-9 in Oral Squamous Cell Carcinoma in Relation with Tumor Depthand Prediction of Lymph Node Metastasis in South of Iraq

The Significance of Vimentinand Matrix Metalloproteinase-9 in Oral Squamous Cell Carcinoma in Relation with Tumor Depthand Prediction of Lymph Node Metastasis in South of Iraq

Immunohistochemical expression of CD44 in oral squamous cell carcinoma in relation to histomorphological parameters and clinicopathological factors.

Oral squamous cell carcinoma (OSCC) is characterised by its variable clinical course. In addition to the routinely used TNM and Union for International Cancer Control systems, patient-specific prognostic/predictive biomarkers are needed. Promising biomarkers include the determination of the cancer stem cell compartment, which can be identified by CD44 expression (among other things). The aim of this study was to evaluate the impact of CD44 in OSCC in terms of correlation with histomorphology, especially targeting features of EMT, and its influence on patient prognosis. A well-characterised cohort of 108 therapy-naive OSCCs with complete long-term follow-up and matched lymph node metastases were evaluated for CD44 expression by immunohistochemistry. CD44 expression was correlated with histomorphological characteristics (including tumour differentiation and tumour budding), clinicopathological parameters, and follow-up data. Overexpression of CD44 was detected in 37% of OSCCs within the tumour centre, in 39% of OSCCs at the invasive margin, and in 16% of lymph node metastases. CD44 overexpression at the invasive margin was significantly correlated with poor histopathological differentiation, and specifically with high tumour budding activity and single-cell invasion as signs of epithelial-mesenchymal transition (EMT). CD44 overexpression within the tumour core region and in lymph node metastases was identified as an independent prognostic factor for poor overall, disease-specific and disease-free survival in subsets of patients with advanced OSCC. Our study demonstrates the association of CD44 with tumour aggressiveness and EMT, as well as the independent prognostic impact of CD44 in a subset of OSCCs, which underlines the role of tumour cell stemness as a key factor in malignant behaviour in this disease.

An alternative way to measure the depth of invasion of vulvar squamous cell carcinoma in relation to prognosis

Depth of invasion is an important prognostic factor for patients with vulvar squamous cell carcinoma. The aim of this study was to identify the most optimal method of measuring the depth of invasion in relation to the individual outcome in patients with vulvar squamous cell carcinoma. Data of 175 consecutive patients with a primary vulvar squamous cell carcinoma with known lymph node status, treated in the Radboud University Medical Center, the Netherlands (2000–2010), were stored in a database. At pathology review of 148 (85%) cases, depth of invasion was measured using the conventional and alternative methods. Clinical and pathological characteristics of patients with a change in FIGO stage were compared with those without a change in stage. In 148 vulvar squamous cell carcinoma patients, the median depth of invasion was shown to be decreased from 5.5 mm (range 1.1–20) using the conventional method to 3.6 mm (range 0.2–20) using the alternative method (P<0.05). This led to a change in the FIGO stage in 13 of the 148 (9%) patients and a change in depth of invasion from 3.5 to 0.2 mm in one patient (1%) with FIGO stage IIIA. Of all 69 stage 1B patients, 13 (19%) were downstaged to stage IA. The downstaged patients developed less recurrences (15% vs 39%) and had a higher disease-specific survival (100% vs 84%) compared with the patients who remained FIGO stage IB. Using the alternative method for measuring the depth of invasion in tumors of vulvar squamous cell carcinoma patients, 19% of the patients with a FIGO stage IB tumor might be treated without groin surgery resulting in less treatment-related morbidity. The results are promising but more prospective data on a higher number of patients are necessary.

Reproducibility of Histopathological Diagnosis in Poorly Differentiated NSCLC: An International Multiobserver Study

The 2004 World Health Organization classification of lung cancer contained three major forms of non-small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non-small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis. Resection specimens (n = 37) with SqCC, large cell carcinoma, basaloid carcinoma, sarcomatoid carcinoma, lymphoepithelial-like carcinoma, and solid AdC, were contributed by the participating pathologists. Hematoxylin and eosin (H&E) stained slides were digitized. The diagnoses were evaluated in two ways. First, the histological criteria were evaluated and the (differential) diagnosis on H&E alone was scored. Second, the added value of additional stains to make an integrated diagnosis was examined. The histologic criteria defining SqCC were consistently used, but in poorly differentiated cases they were infrequently present, rendering the diagnosis more difficult. Kappa scores on H&E alone were for SqCC 0.46, large cell carcinoma 0.25, basaloid carcinoma 0.27, sarcomatoid carcinoma 0.52, lymphoepithelial-like carcinoma 0.56, and solid AdC 0.21. The κ score improved with the use of additional stains for SqCC (combined with basaloid carcinoma) to 0.57, for solid AdC to 0.63. The histologic criteria that may be used in the differential diagnosis of poorly differentiated lung cancer were more precisely refined. Furthermore, additional stains improved the reproducibility of histological diagnosis of SqCC and AdC, uncovering information that was not present in routine H&E stained slides.