“CASE SERIES OF EGFR MUTATIONS IN SQUAMOUS CELL CARCINOMA LUNG ” Agrawal Chaturbhuj, Saini Rajeev, Koyyala V Pradeep Babu, Batra Ullas, Jain Akhil INTRODUCTION Lung cancer is the leading cause of cancer-related death worldwide Advances in molecular biology have unveiled various targetable mutations with EGFR being most common ,testing of which is recommended for all locally advanced or metastatic adenocarcinoma lung but recommendation in squamous histology is controversial. However, higher incidence of EGFR mutation was found in females, never smokers and Asians. We report two cases with squamous cell lung cancer in non smoker females with EGFR mutations emphasizing the importance of testing in such population. The identification of mutations within the epidermal growth factor receptor (EGFR), and the finding that these mutations make tumors exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs), has revolutionized treatment of non-small-cell lung cancer (NSCLC). CASE DETAILS CASE 2 : 44 years old female, diabetic, hypertensive, non smoker PRESENTING SYMPTOMS: Breathlessness and Cough with occasional hemoptysis. EVALUATION: Bronchoscopy: Malignant intermediate bronchus obstruction. Bronchial biopsy : Squamous cell carcinoma (IHC: p40+ , TTF1 negative ) PET CT: Lung mass with bony, lymph nodal metastasis TREATMENT: Chemotherapy (3 cycles of Gemcitabine and cisplatin) After 3 cycles of chemotherapy: Partial response In view of her being non smoker, female of younger age group, EGFR mutation analysis was done It came positive for exon 21 (L858R) Mutation. Patient was started on erlotinib wef 02/12/14 At 3 months follow up – PET CT: Excellent response to treatment Presently patient is on regular follow up and on Tab Erlotinib CASE 1 : 56 years old female, diabetic, hypertensive, non smoker PRESENTING SYMPTOMS: cough, weight loss and right sided weakness. EVALUATION: MRI BRAIN: 2 hypodense lesions in left frontal lobe. PET CT: Right lung mass with mediastinal lymph Nodes ,brain, adrenal, pancreatic and bone lesions. CORE NEEDLE BIOPSY (LUNG MASS): Squamous cell carcinoma (p40 + , TTF –) TREATMENT: Whole brain radiotherapy followed by 2 cycles of chemotherapy (gemcitabine and carboplatin) RESPONSE: Poor tolerability due to grade 4 neutropenia Poor performance status  chemotherapy could not be given further Her biopsy was reassessed for EGFR mutational analysis and showed L858R mutation positive. She was started on erlotinib and imaging studies after 2 months of therapy demonstrated significant tumor response in the pulmonary lesions as well as in metastatic sites. Presently 5 months follow up – Patient asymptomatic and on regular follow Good compliance to erlotinib with no major side effects ECOG performance status at diagnosis Tumor cells showing immunopositivity for p40 Tumor cells showing immunopositivity for p40 Tumor cells showing immunopositivity for TTF 1 DISCUSSION Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in the progression to metastatic disease. EGFR  one of the most common targetable mutation in NSCLC (particularly in non squamous histology. The incidence of EGFR mutations in NSCLC varies by ethnicity, with studies estimating a range from 10-15% of Caucasians to 40-50% of Asians. 1 EGFR positivity occurs in less than 5% patients of squamous cell histology. Detection of EGFR mutations will mark excellent response with treatment with EGFR inhibitor targeted therapy. Thus patient should not be deprived of potentially beneficial therapies,only basing on histology , especially in light of some important caveats regarding exclusion of testing in all cases diagnosed as squamous cell carcinoma. First, a small biopsy sample showing squamous morphology does not exclude the possibility of an adenocarcinomatous component elsewhere in the lesion. 2 Second, the distinction between adenocarcinoma and squamous cell carcinoma can be extremely challenging in some cases3. EGFR mutations have been found to be more common in female patients, never-smokers, and patients of Asian ethnicity4. Thus, such patients even with squamous histology should be tested for EGFR mutation. REFERENCES Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J. 2010;277(2):301–308. Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res.2012;18:1167–1176 Thunnissen E, Kerr KM, Herth FJ, et al. The challenge of NSCLC diagnosis and predictive analysis on small samples: practical approach of a working group.Lung Cancer. 2012;76:1–18 Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009; 361:958–967