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FOXM1 is a transcription factor that controls cell cycle regulation, cell proliferation, and differentiation. Overexpression of FOXM1 has been implicated in various cancer types. However, the activation status and functional significance of FOXM1 in diffuse large B cell lymphoma (DLBCL) have not been well investigated. Using proteomic approaches, we discovered that the protein expression levels of FOXM1 and PLK1 were positively correlated in DLBCL cell lines and primary DLBCL. Expression levels of FOXM1 and PLK1 mRNAs were also significantly higher in DLBCL than in normal human B cells and could predict poor prognosis of DLBCL, particularly in patients with germinal center B cell-like (GCB) DLBCL. Furthermore, proteomic studies defined a FOXM1-PLK1 signature that consisted of proteins upstream and downstream of that axis involved in the p38-MAPK-AKT pathway, cell cycle, and DNA damage/repair. Further studies demonstrated a mechanistic function of the FOXM1/PLK1 axis in connection with the DNA damage response pathways regulating the S/G2 checkpoint of the cell cycle. Therapeutic targeting of FOXM1/PLK1 using a FOXM1 or PLK1 inhibitor, as well as other clinically relevant small-molecule inhibitors targeting ATR-CHK1, was highly effective in DLBCL in vitro models. These findings are instrumental for lymphoma drug discovery aiming at the FOXM1/PLK1/ATR/CHK1 axis.

Additional file 1: Supplementary Figure 1. Distinct mutational profiles are seen across primary tumor and synchronous metastases. Supplementary Figure 2. Distinct T cell repertoire metrics between tumors from patients in localized non-small cell lung cancer (NSCLC, PROSPECT cohort) and our patient. Supplementary Figure 3. Distinct T cell repertoire metrics between thoracic and non-thoracic tumors but no differences in relation to lymph node involvement. Supplementary Figure 4. Distinct antigenic profiles are associated with left-side thoracic tumors. Supplementary Figure 5. A higher TCR Jaccard index (JI) in our patient compared to a previously published multi-region localized non-small cell lung cancer (NSCLC). Supplementary Figure 6. Characterization of shared T cell clonotype proportions and percentages by all 20 tumors. Supplementary Figure 7. Immune cell fractions in left-side thoracic tumors versus non-left side thoracic tumors. Supplementary Figure 8. Positive correlations of CD8 to Treg ratio with TCR metrics. Supplementary Table S1. Sample information. Supplementary Data. TCR rearrangements.

It is sometimes difficult to differentiate between type B3 thymoma from thymic carcinoma histologically. Given the rarity of these tumours, studies have been limited. A series of 66 thymic neoplasms were reviewed and classified according to the World Health Organization (WHO) scheme. We performed a tissue microarray analysis of surgically resected thymic tumour specimens including 12 thymic carcinomas, 17 type B3 thymomas and 37 thymomas of other types. Percentage and staining intensity of immunohistochemical markers were recorded. Tumour eosinophilia was recorded positive if at least one eosinophilic cell identified. Positive staining of the following markers significantly differentiated type B3 thymoma from thymic carcinoma: cytokeratin 5/6 (15 vs. 3), Mesothelin (0 vs. 5), cytoplasmic androgen receptor (10 vs. 0), CD57 (9 vs. 0), CD5 (0 vs. 7), TdT (lymphocytic) (14 vs. 1), CD1a (lymphocytic) (14 vs. 2), CD117 (1 vs. 9), MOC31 (2 vs. 6), p21 (2 vs. 8), cytoplasmic Survivin (0 vs. 4), and tumour eosinophilia (1 vs. 11). Combining two or three markers was able to differentiate these two tumours with area under the curve percentage of at least 92%. Tumour eosinophilia combined with a panel of immunohistochemistry could differentiate type B3 thymoma from thymic carcinoma.

Gastric cancer is a disease of gene-environment interactions, as suggested by the varying geographic patterns of its incidence. Even in areas with high rates of Helicobacter pylori infection, only a small proportion of infected individuals develop gastric cancer. Genetic susceptibility to gastric cancer can be investigated by common genetic variants, such as single nucleotide polymorphisms (SNPs), in various genes that regulate multiple biological pathways. The susceptibility to gastric carcinogenesis has a substantial influence on the population attributable risk by modulating the effects of environmental risk factors. Despite recent progress in the field of the molecular epidemiology of cancer, a re-evaluation of gastric cancer susceptibility and potentially functional SNPs in candidate genes is necessary, given the inconsistency of previous reported studies. This review focuses on genetic variants that contribute to the etiology of gastric cancer, particularly those SNPs involved in inflammatory response, metabolism of chemical carcinogens, DNA repair, and tumor suppression. In the future, well-designed large multicenter population-based studies will be needed to validate current findings and provide the rationale for identifying at-risk subpopulations for primary prevention of gastric cancer.

Diagnosis and classification of lung and pleural neoplasms are complex due to diverse histopathology and tumor heterogeneity. A large number of immunohistochemical markers have recently become available to facilitate accurate diagnosis and classification of pulmonary and pleural neoplasms. The purpose of this article is to review the current data available on these markers and to provide a practical approach to evaluate pulmonary and pleural neoplasms immunohistochemically. Current literature of immunohistochemical markers related to pulmonary and pleural neoplasms was collected and reviewed. Literature emphasizing differential diagnosis was selected. Data useful in the diagnosis and classification of pulmonary and pleural neoplasms was collated. This review provides an updated overview and general guideline for the practicing surgical pathologists to resolve some of the common differential diagnostic situations in their daily immunohistochemical assessment of pulmonary and pleural neoplasms.

Nuclear matrix proteins (NMPs) are important diagnostic and prognostic markers in various human cancers. The hHpr1/p84/Thoc1 protein, a key NMP, resides in the nuclear matrix and is involved in the human TREX complex, which is required for regulation of transcription elongation, pre-RNA splicing, and mRNA export of a subset of human genes. Depletion of hHpr1/p84/Thoc1 decreases growth rates in multiple cancer cell lines, and the expression levels of hHpr1/p84/Thoc1 are strongly associated with tumor size and aggressiveness of several human cancers. Little is known about the expression of this protein in human non-small cell lung cancer (NSCLC) and its association with patients’ clinicopathologic characteristics and prognosis. We evaluated hHpr1/p84/Thoc1 expression in 133 NSCLC patients by immunohistochemistry of tissue microarrays using paraffin-embedded tumor tissue and we confirmed the tissue staining by Western blot analysis. The prognostic significance of hHpr1/p84/Thoc1 expression in tumor tissue was assessed by the Cox proportional hazards regression model. Expression of hHpr1/p84/Thoc1 was found in 51% of patients, and was more prevalent in males than females (59% vs 43%, p = 0.07) and in blacks than whites (91% vs 48%, p = 0.009). In survival analysis, hHpr1/p84/Thoc1 expression appeared to be weakly associated with elevated risk of death among patients with stage I tumors (RR = 1.53, 95% CI = 0.85-2.77, p = 0.16), squamous cell carcinomas (RR = 1.75, 95% CI = 0.73-4.21, p = 0.21), and family histories of lung cancer (RR = 1.55, 95% CI = 0.81-2.97, p=0.18), although none of these associations was statistically significant. Thus elevated expression of hHpr1/p84/Thoc1 is common in NSCLC and may have prognostic significance in subgroups of patients. Further studies with larger sample size are needed to elucidate the role of this critical nuclear matrix protein in NSCLC prognosis.

Tailgut cysts are uncommon developmental cysts that form in the presacral space. Complications of tailgut cysts include benign reactive lesions associated with infection and inflammation, and malignant transformation. Six cases of carcinoid tumor arising in tailgut cysts have been reported in the medical literature to date. Here we report another case of carcinoid tumor arising in a tailgut cyst. Because six of seven cases occurred in females, we postulate that these tumors are hormone-associated. This hypothesis is supported by the present study. We found strong estrogen receptor immunoreactivity of the benign squamous and columnar cyst-lining cells as well as carcinoid tumor cells, in addition to neuroendocrine differentiation in the tumor cells and scattered cyst-lining cells. We speculate that estrogen receptor may be a potential therapeutic target in patients with this condition.

Background Malignant granular cell tumor (MGCT) is a rare disease entity. Forty-one well-documented MGCTs have been reported in the world literature. Case Report This report describes a patient who presented with a MGCT of the lung and reviews the preoperative evaluation, pathologic features and differential diagnosis of the disease. This case represents the first report of resected primary pulmonary MGCT. Conclusions Diagnosis of MGCT is based on histology of the primary tumor, immunohistochemistry, and exclusion of tumors that may mimic granular cell tumor.