Kirsten rat sarcoma virus protein overexpression in adenocarcinoma lung: Association with clinicopathological and histomorphological features

Rahul Kumar Pandey; Saumya Shukla; Rahat Hadi; Nuzhat Husain; Mohammad Hayatul Islam; Ashish Singhal; Surya Kant Tripathi; Rajiv Garg

doi:10.4103/jcar.JCar_11_20

Kirsten rat sarcoma virus protein overexpression in adenocarcinoma lung: Association with clinicopathological and histomorphological features

J Carcinog. 2020 Oct 8:19:9. doi: 10.4103/jcar.JCar_11_20. eCollection 2020.

Authors

Rahul Kumar Pandey^{1

2}, Saumya Shukla¹, Rahat Hadi³, Nuzhat Husain¹, Mohammad Hayatul Islam², Ashish Singhal⁴, Surya Kant Tripathi⁵, Rajiv Garg⁵

Affiliations

¹ Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
² Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
³ Department of Radiation Oncology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
⁴ Department of Surgical Oncology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
⁵ Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India.

Abstract

Context: Lung cancer is the leading cause of cancer-related deaths worldwide. The constitutive activation of multiple signaling pathways is the major cause of carcinogenesis.

Aims: The study evaluates the frequency of Kirsten rat sarcoma virus (KRAS) protein overexpression and correlates with clinicopathological and histomorphological features in non-small cell lung carcinoma (NSCLC)-adenocarcinoma.

Settings and design: Tertiary hospital-based retrospective and prospective case series included 100 cases of NSCLC-adenocarcinoma.

Materials and methods: The basic panel of Immunohistochemistry including Napsin-A, thyroid transcription factor-1 (TTF-1), and markers for squamous differentiation, p-40 was used in formalin-fixed paraffin-embedded tissue blocks. The KRAS monoclonal antibody (9.13, Thermo Fisher Scientific, USA) was used.

Statistical analysis used: The IBM-Statistical Package for the Social Sciences (SPSS) (SPSS, International Business Machines Corporation, New York, NY, USA) analysis software, version 16 was used for all statistical calculations.

Results: KRAS protein expressed in 28.0% (28/100) cases. Cases were grouped as KRAS positive and negative. TTF-1 and Napsin-A were expressed in 89.25% (n = 25) and 92.86% (n = 26) cases, respectively. Stage IV clinical disease was identified in 55% of cases, and 36.84% of cases had a mean survival between 6 and 12 months. In KRAS positive group, the most common pattern of cellular arrangement was acinar/loose clusters pattern present in 64.29% (n = 21) and 75.0% (n = 18) cases followed by the solid pattern present in 42.86% of cases (n = 12), respectively. Necrosis was identified in 57.14% (n = 16) cases. Mucin pattern was present in 32.14% of cases (n = 9), which was significantly different when compared with the KRAS negative group (P = 0.036).

Conclusions: This finding may imply that KRAS mutations may not be entirely triggered by alterations induced by carcinogens in smoke. KRAS gene is frequently mutated in pulmonary tumors. It should be tested in NSCLC owing to its predictive and prognostic effects.

Keywords: Histomorphology; Kirsten rat sarcoma virus; non-small cell lung carcinoma-adenocarcinoma; thyroid transcription factor-1.