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57 Squamous cell and adenocarcinoma ‘lineage’ markers in large cell carcinoma of the lung
Posters, 10th Annual British Thoracic Oncology Group Conference, 2012: Diagnosis and Staging since they represent an overlapping mixture of proteins, lipids, carbohydrates, DNA and cellular metabolites. Method: 42 biopsy specimens were obtained bronchoscopically from 24 patients representing 16 normal biopsies, 6 with low grade dysplasia, 15 with high grade dysplasia and 5 invasive squamous cell carcinomas. Matched histopathological samples were examined by H&E staining and microscopy for pathological classification. In all cases, IR data were collected in the 4000 900 cm 1 region using a Bruker IFS66s FTIR spectrometer. Results: There were minimal changes to differentiate low grade changes from normal epithelial cells however there were significant and reproducible changes corresponding to high grade dysplasia and cancer. We have developed an algorithm analysing the relative size of IR peaks in the 1290 1270 cm 1 range that differentiates with 100% accuracy between normal/low grade and high grade/cancer in this small pilot study. Conclusions: • High quality mid-IR spectra of biopsy specimens reveal differences between pathological groups. • This technology has the potential to provide real-time near patient cytopathological diagnosis for the bronchoscopist or thoracic surgeon for instance to confirm clear resection margins. • Identification of the chemical changes occurring at a cellular level may lead to reverse translation and better understanding of the processes driving progression to malignant transformation. • Future work will refine and validate the observed changes. 57 Squamous cell and adenocarcinoma ‘lineage’ markers in large cell carcinoma of the lung K.M. Kerr *, R. Barr, P.S. Loo, N. Fyfe, M. Nicolson. Aberdeen Royal Infirmary, Aberdeen, UK Introduction: The recognition that adenocarcinomas and squamous cell carcinomas show differences in either response or toxicity to particular targeted agents have placed a premium on accurate pathological classification on cases before therapy. In most instances, such a diagnosis is based upon classification of small diagnostic samples and the immunohistochemical (IHC) expression of so-called lineage markers is often used to predict the likely differentiated histology in small undifferentiated samples (NSCLCNOS). Some lung cancers are, of course, truly and totally undifferentiated and in the context of surgical resection cases, are reported as large cell (LCC) or sarcomatoid (SARC) undifferentiated carcinomas. This study aimed to elucidate the expression of these lineage markers in such surgically resected undifferentiated carcinomas of the lung (LCC and SARC), which may imply biological similarity between undifferentiated tumours and their differentiated counterparts. Method: In total, 76 LCC and 35 sarcomatoid carcinomas underwent immunohistochemical analysis with TTF-1 and Napsin A (adenocarcinoma lineage markers) and Cytokeratin 5/6, p63 and Desmocollin-3 (squamous cell carcinoma lineage markers). The intensity and the extent of staining of each antibody in all cases were assessed using light microscopy by two independent observers (RB, KMK). Results: Most of the cases showed an antibody profile consistent with that found in adenocarcinoma (18.9%) or squamous cell carcinoma (53.2%). A significant proportion showed conflicting antibody positivity (16.2%) whilst a small proportion showed complete negativity to all the markers (11.7%). Conclusions: Many LCC and SARC share lineage marker expression with differentiated NSCLC and supports dedifferentiation as a possible pathogenesis for undifferentiated lung cancer. This may also mean that these undifferentiated tumours will show similar responses to targeted therapy as seen in differentiated NSCLC.
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58 Antibody independent micro-filtration biochip for the diagnosis of lung cancer A. Tay1 *, A. Nicholson1,2 , J. von der Thusen1,2 , V. Anikin2 , T. Tetley1 , E. Lim1,2 . 1 Imperial College, National Heart and Lung Institute, London, UK, 2 Royal Brompton and Harefield Hospital, London, UK Introduction: The majority of currently available technology to isolate circulating tumour cells (CTCs) involves the use of antibodies targeting the epithelial cell adhesion molecule (e.g. Veridex Cell Search System). We describe initial results using conventional clinical criteria with haematoxylin and eosin staining to identify CTCs. Method: Samples of blood were collected and processed from patients who had consented to donate blood for research (NRES 10/H0504/9). Samples were reviewed by two pathologists and between pathologist agreement was estimated using kappa statistic. Weighted sensitivity (either pathologist classify “suspicious” or “cancer”) and specificity (both pathologists classify “cancer”) analyses were undertaken to help position the technology in clinical practice. Results: From March to October 2011, 52 samples of blood was collected and processed from patients who had consented to donate blood for research (NRES 10/H0504/9). Of 52 samples, 4 were from patients that did not have cancer, 35 from patients with primary lung cancer and 11 from patients with secondary lung cancer. Agreement between the two pathologists was 73%, with a kappa value of 0.58 (95% CI: 0.26, 0.91) indicating moderate agreement. Sensitivity weighted analysis test performance was sensitivity 33% (20 to 48) and specificity 50% (7 to 93), whilst specificity weighted test performance was sensitivity 13% (5 to 25) and specificity 100% (49 to 100). Conclusions: Initial results suggest this as a promising marker for the diagnosis of lung cancer with high specificity (positive test rules in disease). Confidence intervals remain wide and a corroborative clinical study will be required to evaluate the test performance in a clinical (cancer network) setting. 59 The use of immunohistochemistry in sub-typing non-small cell lung cancer (NSCLC) and reducing the rate of NSCLC not otherwise specified (NSCLC NOS) N. Skehan *, C. Thomas, N. McAndrew. Department of Respiratory Medicine, Wrexham Maelor Hospital, Wrexham, UK Introduction: The chemotherapeutic treatments for adenocarcinoma and squamous cell carcinoma of the lung now differ considerably, rendering distinction between these cell types of considerable clinical relevance. The Royal College of Pathologists (RCPath) now recommends the routine use of immunohistochemistry (IHC) where sub-typing is not clear by morphology alone. We reviewed the histological diagnosis of NSCLC at Wrexham Maelor Hospital with respect to the above for patients first seen in 2008 and 2009. Method: Review of histology reports of the relevant cases of NSCLC, recording diagnosis after light microscopy, overall rates of IHC and IHC usage by individual pathologists. Results: 140 new cases of histologically proven NSCLC were identified (2008 n = 77, 2009 n = 63). Following light microscopy 32/77 (42%) and 35/63 (56%), respectively, remained NSCLC NOS. Of these, 22 (69%) in 2008 and 27 (77%) in 2009 proceeded to IHC. Following IHC there was accurate sub-typing in 13 of 22 (41%) in 2008, and 22 of 27 (62%) in 2009. The final rates of NSCLC NOS were 31% (2008) and 23% (2009). There was wide variation in the use of IHC by pathologists. Of the 4 reporting pathologists, Pathologist 1 reviewed 36% of cases of NSCLC and requested 61% of IHC, whereas Pathologist 3 reviewed 23% of cases, only requesting 4% of IHC. Conclusions: NSCLC NOS rates in Wrexham were high in 2008 and 2009, and usage of IHC between pathologists varied. However,
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58 Antibody independent micro-filtration biochip for the diagnosis of lung cancer A. Tay1 *, A. Nicholson1,2 , J. von der Thusen1,2 , V. Anikin2 , T. Tetley1 , E. Lim1,2 . 1 Imperial College, National Heart and Lung Institute, London, UK, 2 Royal Brompton and Harefield Hospital, London, UK Introduction: The majority of currently available technology to isolate circulating tumour cells (CTCs) involves the use of antibodies targeting the epithelial cell adhesion molecule (e.g. Veridex Cell Search System). We describe initial results using conventional clinical criteria with haematoxylin and eosin staining to identify CTCs. Method: Samples of blood were collected and processed from patients who had consented to donate blood for research (NRES 10/H0504/9). Samples were reviewed by two pathologists and between pathologist agreement was estimated using kappa statistic. Weighted sensitivity (either pathologist classify “suspicious” or “cancer”) and specificity (both pathologists classify “cancer”) analyses were undertaken to help position the technology in clinical practice. Results: From March to October 2011, 52 samples of blood was collected and processed from patients who had consented to donate blood for research (NRES 10/H0504/9). Of 52 samples, 4 were from patients that did not have cancer, 35 from patients with primary lung cancer and 11 from patients with secondary lung cancer. Agreement between the two pathologists was 73%, with a kappa value of 0.58 (95% CI: 0.26, 0.91) indicating moderate agreement. Sensitivity weighted analysis test performance was sensitivity 33% (20 to 48) and specificity 50% (7 to 93), whilst specificity weighted test performance was sensitivity 13% (5 to 25) and specificity 100% (49 to 100). Conclusions: Initial results suggest this as a promising marker for the diagnosis of lung cancer with high specificity (positive test rules in disease). Confidence intervals remain wide and a corroborative clinical study will be required to evaluate the test performance in a clinical (cancer network) setting. 59 The use of immunohistochemistry in sub-typing non-small cell lung cancer (NSCLC) and reducing the rate of NSCLC not otherwise specified (NSCLC NOS) N. Skehan *, C. Thomas, N. McAndrew. Department of Respiratory Medicine, Wrexham Maelor Hospital, Wrexham, UK Introduction: The chemotherapeutic treatments for adenocarcinoma and squamous cell carcinoma of the lung now differ considerably, rendering distinction between these cell types of considerable clinical relevance. The Royal College of Pathologists (RCPath) now recommends the routine use of immunohistochemistry (IHC) where sub-typing is not clear by morphology alone. We reviewed the histological diagnosis of NSCLC at Wrexham Maelor Hospital with respect to the above for patients first seen in 2008 and 2009. Method: Review of histology reports of the relevant cases of NSCLC, recording diagnosis after light microscopy, overall rates of IHC and IHC usage by individual pathologists. Results: 140 new cases of histologically proven NSCLC were identified (2008 n = 77, 2009 n = 63). Following light microscopy 32/77 (42%) and 35/63 (56%), respectively, remained NSCLC NOS. Of these, 22 (69%) in 2008 and 27 (77%) in 2009 proceeded to IHC. Following IHC there was accurate sub-typing in 13 of 22 (41%) in 2008, and 22 of 27 (62%) in 2009. The final rates of NSCLC NOS were 31% (2008) and 23% (2009). There was wide variation in the use of IHC by pathologists. Of the 4 reporting pathologists, Pathologist 1 reviewed 36% of cases of NSCLC and requested 61% of IHC, whereas Pathologist 3 reviewed 23% of cases, only requesting 4% of IHC. Conclusions: NSCLC NOS rates in Wrexham were high in 2008 and 2009, and usage of IHC between pathologists varied. However,