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1. Jena Song, DO, MPH* 2. Jose Bustillo, DO* 3. Sherin Meledathu, DO* 1. *Department of Internal Medicine and Pediatrics, Newark Beth Israel Medical Center and Children’s of New Jersey, Newark, NJ A full-term, large for gestational age newborn girl, is born via vaginal delivery to a 32-year-old gravida 3, para 3 mother with a generally uncomplicated pregnancy. The pediatrics team has been called to the delivery for meconium-stained amniotic fluid. The infant does not appear to be in respiratory distress and has Apgar scores of 9 and 9 at 1 and 5 minutes, respectively. Her blood glucose level is 45 mg/dL. Upon inspection, she is noted to have a large, raised, hyperpigmented plaque covering the right side of her head, measuring 18 × 15 cm (Figs 1 and 2). This plaque is accompanied by greater than 20 other macules, patches, and plaques diffusely distributed throughout the body that are either hyper or hypopigmented, have either smooth or irregular borders, and vary in size from 0.5 to 3 cm (Fig 3). The patient also has multiple areas of blue-gray pigmented patches on her sacrum, but no sacral dimple is evident. Her neurologic examination reveals a newborn who is alert, responsive, and has normal primitive reflexes and tone for gestational age. Her head circumference is 35.5 cm (53rd percentile). No dysmorphic features are noted, and the remainder of the examination is remarkable only for a systolic heart murmur. Figure 1. Gross visualization of plaque throughout the body. A large, raised, hyperpigmented plaque, measuring 18 × 15 cm, covering the right side of the infant’s scalp. © 2017–2020, Jena Song, DO, MPH. All rights reserved. Reprinted with permission. Figure 2. Gross visualization of plaque throughout the body. Further visualization of large, hyperpigmented plaque extending to the right maxillary region and right upper eyelid. © 2017–2020, Jena Song, DO, MPH. All rights reserved. Reprinted with permission. Figure 3. Gross visualization of plaque throughout the body. Numerous hyperpigmented macules, patches, and patches of smaller caliber covering the right shoulder, posterior neck, back, …

Background: Current histopathological classification and TNM staging have limited accuracy in predicting survival and stratifying patients for appropriate treatment. The goal of the study is to determine whether the expression pattern of functionally important regulatory proteins can add additional values for more accurate classification and prognostication of non-small lung cancer (NSCLC). Methods: The expression of 108 proteins and phosphoproteins in 30 paired NSCLC samples were assessed using Protein Pathway Array (PPA). The differentially expressed proteins were further confirmed using a tissue microarray (TMA) containing 94 NSCLC samples and were correlated with clinical data and survival. Results: Twelve of 108 proteins (p-CREB(Ser133), p-ERK1/2(Thr202/Tyr204), Cyclin B1, p-PDK1(Ser241), CDK4, CDK2, HSP90, CDC2p34, β-catenin, EGFR, XIAP and PCNA) were selected to build the predictor to classify normal and tumor samples with 97% accuracy. Five proteins (CDC2p34, HSP90, XIAP, CDK4 and CREB) were confirmed to be differentially expressed between NSCLC (n=94) and benign lung tumor (n=19). Over-expression of CDK4 and HSP90 in tumors correlated with a favorable overall survival in all NSCLC patients and the over-expression of p-CREB(Ser133) and CREB in NSCLC correlated with a favorable survival in smokers and those with squamous cell carcinoma, respectively. Finally, the four proteins (CDK4, HSP90, p-CREB and CREB) were used to calculate the risk score of each individual patient with NSCLC to predict survival. Conclusion: In summary, our data demonstrated a broad disturbance of functionally important regulatory proteins in NSCLC and some of these can be selected as clinically useful biomarkers for diagnosis, classification and prognosis.