Sry-related HMg-Box gene 10 (SOX10) is a nuclear transcription factor that plays an important role in melanocytic cell differentiation. It has been shown to be a sensitive marker of melanoma including spindle and desmoplastic subtypes. We assessed its frequency of expression in melanoma, carcinoma, benign nevi, and non-neoplastic tissues with routine immunohistochemistry for SOX10. The 109 primary melanoma included 49 epithelioid, 19 spindle cell, 22 desmoplastic, and 19 mixed spindle cell/desmoplastic melanoma. All primary, except 8 desmoplastic melanoma, and 11 metastatic melanoma were strongly and diffusely nuclear SOX10-positive. Six desmoplastic melanoma had ≤10% cells positive, and 2 were <50% positive, all of 3+ intensity. Eighteen of 149 (12%) breast carcinoma were SOX10-positive. All 24 ovarian, 23 endometrial, 26 lung, and 25 colon carcinoma were SOX10-negative. All 43 benign nevi, 18 dysplastic nevi, 68 non-neoplastic and benign skins, and all 56 non-neoplastic breast tissue were SOX10-positive. The sensitivity and specificity for SOX10 in the diagnosis of melanoma are 1.0 and 0.93, respectively; the positive and negative predictive values are 0.87 and 1.0, respectively. SOX10 is a sensitive, specific marker for melanoma. As benign nevi also express SOX10, it cannot be used to differentiate between benign and malignant pigmented skin lesions. Only a small number of breast carcinoma (12%), and breast lobules, express SOX10; no carcinoma of the ovary, endometrium, lung, or colon expressed SOX10.

Disordered cancer metabolism was described almost a century ago as an abnormal adaptation of cancer cells to glucose utilization especially under hypoxic conditions; the so-called Warburg effect. Greater research interest in this area in the last several decades has led to the recognition of the critical coupling of specific malignant phenotypes such as increased proliferation and resistance to programmed cell death (apoptosis) with altered metabolic handling of key molecules that are essential for normal cellular metabolism. The altered glucose metabolism frequently encountered in cancer cells has been exploited for cancer diagnosis and treatment. More recently, the role of other glycolytic pathway intermediates as well as alternative pathways for energy generation and macromolecular synthesis in cancer cells has become recognized. Especially, the important role of altered glutamine metabolism in the malignant behavior of cancer cells and the potential exploitation of this cellular adaptation for therapeutic targeting has emerged as an important area of cancer research in the last decade. Expectedly, attempts to exploit this understanding for diagnostic and therapeutic ends are running apace with the elucidation of the complex metabolic alterations that accompany neoplastic transformation. Because lung cancer is a leading cause of cancer death with limited curative therapy options, careful elucidation of the mechanism and consequences of disordered cancer metabolism in lung cancer is warranted. This review provides a concise, systematic overview of the current understanding of the role of altered glutamine metabolism in cancer and how these findings intersect with current and future approaches to lung cancer management.

P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the link of their activity to the extrinsic apoptosis pathway and showed that their autophagy modification has a critical stand point in tumorigenesis. These findings explain their vital role in controlling the process of cell death and survival. It has been shown recently that p62 and ubiquitin overexpression in different types of cancers, such as triple negative breast and ovarian cancers, have directly correlated with incidence of distant metastases. We aim to evaluate p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic, and pancreatic origin, and correlate with annotated clinicopathologic data. In gastric carcinoma (61), positive p62 nuclear expression was noted in 57% and cytoplasmic in 61%, while positive ubiquitin was nuclear expressed in 68.8%, and cytoplasmic in 29.5%. In colon carcinoma (45), positive p62 nuclear expression was noted in 29% and cytoplasmic in 71%, while positive ubiquitin was nuclear in 58% and cytoplasmic in 44%. In pancreatic cancer (18), positive p62 nuclear expression was noted in 78% and cytoplasmic in 56%, while positive ubiquitin was nuclear in 83% and cytoplasmic in 72%. Normal gastric (6), colon (4), and pancreatic (4) tissues were negative for both P62 and ubiquitin (nuclear and cytoplasmic staining <20%). Ubiquitin high expression was associated with more lymph node metastases in colon (4.14 vs 1.70, P = 0.04), and pancreatic adenocarcinomas (3.07 vs 0.33, P = 0.03). Also, ubiquitin high expression was associated with worse pancreatic adenocarcinoma overall survival (1.37 vs 2.26 mos, P = 0.04). In addition, gastric cancer patients with high p62 expression tend to have more poorly differentiated grade when compared to those with low expression (21 vs 17, P = 0.04) but less lymph node metastases (2.77 vs 5.73, P = 0.01). P62 and ubiquitin expression did not correlate with other clinicopathologic parameters in gastric, colon or pancreatic denocarcinomas. The results suggest that p62 and ubiquitin are highly expressed in gastric, colonic, and pancreatic carcinomas. High ubiquitin expression was noted to have an impact on number of lymph node metastases in patients with colon and pancreatic adenocarcinomas, but on overall survival only in patients with pancreatic adenocarcinoma. Also, P62 high expression is correlated with poor differentiation, but less lymph node metastases, in gastric carcinoma.