BACKGROUND: The catalytic subunit of telomerase, hTERT (telomerase reverse transcriptase), is one of the most important components of telomerase, and performs a pivotal role in the mechanism underlying the regulation of telomerase activity in cellular immortalization and carcinogenesis. The principal objective of this study was to investigate hTERT expression in patients with non-small cell lung carcinomas (NSCLCs), and to evaluate its clinical significance and association with the expression of p16 and p53. METHODS: Using tissue microarray, the protein expression profiles of hTERT, p16 and p53 were investigated via immunohistochemistry in 167 samples of NSCLCs. RESULTS: Expression was observed in 54.5% (91/167) of the tumors, which were predominantly squamous cell carcinomas. Patients evidencing hTERT expression in their tumors exhibited significantly poorer survival rates than did patients without hTERT expression in early-stage NSCLCs (p=0.0125). According to the results of our Cox regression analysis, hTERT expression proved to be an independent prognostic factor (p=0.006), particularly for squamous cell carcinomas (p=0.019). hTERT expression was not correlated with p16 expression, but was rather associated with the expression of p53 (p=0.002). CONCLUSIONS: Our results show that hTERT may perform a function in the progression of NSCLC, and that its detection may be useful in predicting the prognosis of NSCLC patients in the early stages of the disease, as well as in the development of a targeted therapy in these tumors.
Carcinogenesis ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Catalytic Domain ; Humans ; Immunohistochemistry ; Lung* ; Prognosis ; Survival Rate ; Telomerase*

Translocations involving chromosome 21q22 are frequently observed in hematologic malignancies including acute myeloid leukemia (AML), most of which have been known to be involved in malignant transformation through transcriptional dysregulation of Runt-related transcription factor 1 (RUNX1) target genes. Nineteen RUNX1 translocational partner genes, at least, have been identified, but not Homeobox A (HOXA) genes so far. We report a novel translocation of RUNX1 into the HOXA gene cluster in a 57-year-old female AML patient who had been diagnosed with myelofibrosis 39 months ahead. G-banding showed 46,XX,t(7;21)(p15;q22). The involvement of RUNX1 and HOXA genes was confirmed by fluorescence in situ hybridization.
Core Binding Factor Alpha 2 Subunit ; Female ; Fluorescence ; Genes, Homeobox ; Hematologic Neoplasms ; Humans ; In Situ Hybridization ; Leukemia, Myeloid, Acute* ; Middle Aged ; Multigene Family* ; Primary Myelofibrosis

BACKGROUND: The p73 is a recently identified homologue of the tumor suppressor gene, p53, and it has been found to induce apoptosis and inhibit cell proliferation. However, its role in the development of tumors is unclear. This study examined the expression of p73 in patients with non-small cell lung carcinomas (NSCLCs) to determine its clinical significance and association with the expressions of p53, pRb, and mdm2. METHODS: A total of 183 NSCLCs were analyzed immunohistochemically using a tissue microarray. RESULTS: The p73 protein was expressed in the cell nuclei in 156 (85.2%) out of the 183 cases. There was no correlation between the p73 expression and the clinicopathological variables. However, there was a correlation between the p73 expression and the mdm2 and pRb expressions. Multivariate Cox survival analysis identified tumor size and lymph node metastasis to be independent prognostic factors, but the p73 expression was not found to be associated with the patients' survival. CONCLUSIONS: p73 is commonly expressed in NSCLC and it might, in conjunction with pRb and mdm2, be involved in the development of these tumors.
Apoptosis ; Carcinoma, Non-Small-Cell Lung ; Cell Nucleus ; Cell Proliferation ; Genes, Tumor Suppressor ; Humans ; Lung* ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis

Early gastric mucosa-associated lymphoid tissue (MALT) lymphoma is considered as an antigen-dependent disease associated with long standing antigenic stimulation by Helicobacter pylori (H. pylori) which induces chronic immune response and lymphoid tissue development at the gastric mucosa normally devoid of lymphoid tissue. With disease progression, antigen-independent clones occur via genetic alterations inducing aberrant activation of nuclear factor kappaB (NF-kappaB) pathway which is essential for regulation of normal lymphocyte development and activation. Four major translocations, including t (11;18)/API2-MALT1, t (1;14)/BCL10-IGH, t (14;18)/(IGH-MALT1 and t (3;14)/FOXP1-IGH, occur mutually exclusively and lead to generation of cIAP2-MALT1 fusion protein or overexpression of BCL10, MALT1 and Foxp1. Translocation t (3;14)(q27;q32)/BCL6-IGH and t (1;2)(p22;p12)/BCL10-IGkappaL also occur in some MALT lymphomas. Mutational inactivation of A20, global NF-kappaB inhibitor, involve the development of especially translocation-negative MALT lymphoma. Downstream effects of most genetic alteration converge on the same NF-kappaB mediated oncogenic pathway. This review discusses the current advances in the pathophysiology underlying the development of gastric MALT lymphoma and its progression.
Clone Cells ; Disease Progression ; Gastric Mucosa ; Helicobacter pylori ; Lymphocytes ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone ; NF-kappa B

Background: Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished. Methods: This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery. Results: Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT. Conclusion This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

PURPOSE: Frozen sections of breast specimens can be used to determine malignancy in a suspected lesion of the breast during operation. However, this procedure always has a potential risk of reporting a false positive or negative. This study was performed to evaluate the accuracy of the frozen section diagnosis of breast lesions. METHODS: A retrospective study to comparing the results of frozen and paraffin, section diagnosis was undertaken. RESULTS: 178 frozen breast section diagnoses were made between January 1995 and December 1996 at Kangnam St. Mary hospital. There were no false positive reports (0%) but 3 false negative reports (1.7%). The causes of a false negative were sampling error in 2 cases and interpretation error in the other. The sensitivity and specificity of the frozen section diagnosis were 94.5 and 99.2%, respectively. CONCLUSION: Despite the high sensitivity and specificity of the breast specimen frozen section diagnosis, care should be taken when making a decision on the frozen section diagnosis due to the possibility of false negative results.
Breast Neoplasms ; Breast* ; Diagnosis* ; Frozen Sections* ; Paraffin ; Retrospective Studies ; Selection Bias ; Sensitivity and Specificity

BACKGROUND: Inter-observer and intra-observer variation in histologic tumor grading are well documented. To determine whether histologic disorderliness in the arrangement of tumor cells may serve as an objective criterion for grading, we tested the hypothesis the degree of disorderliness is related to the degree of tumor differentiation on which tumor grading is primarily based. METHODS: Borrowing from the statistical thermodynamic definition of entropy, we defined a novel mathematical formula to compute the relative degree of histologic disorderliness of tumor cells. We then analyzed a total of 51 photomicrographs of normal colorectal mucosa and colorectal adenocarcinoma with varying degrees of differentiation using our formula. RESULTS: A one-way analysis of variance followed by post hoc pairwise comparisons using Bonferroni correction indicated that the mean disorderliness score was the lowest for the normal colorectal mucosa and increased with decreasing tumor differentiation. CONCLUSIONS: Disorderliness, a pathologic feature of malignant tumors that originate from highly organized structures is useful as an objective tumor grading proxy in the field of digital pathology.
Adenocarcinoma ; Colonic Neoplasms ; Entropy ; Humans ; Mucous Membrane ; Neoplasm Grading ; Observer Variation ; Pathology ; Proxy ; Thermodynamics

BACKGROUND: Recent clinical observation reported that there was a significant correlation between change in circulating vascular endothelial growth factor (VEGF) levels and the occurrence of severe acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the action mechanisms of VEGF in GVHD have not been demonstrated. METHODS: This study investigated whether or not blockade of VEGF has an effect on acute GVHD in a lethally irradiated murine allo-HSCT model of B6 (H-2b)-->B6D2F1 (H-2b/d). Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 (50 microg/dose) or control diluent every other day for 2 weeks (total 7 doses). RESULTS: Administration of the dRK6 peptide after allo-HSCT significantly reduced survival with greaterclinical GVHD scores and body weight loss. Allogeneic recipients injected with the dRK6 peptide exhibited significantly increased circulating levels of VEGF and expansion of donor CD3+ T cells on day +7 compared to control treated animals. The donor CD4+ and CD8+ T-cell subsets have differential expansion caused by the dRK6 injection. The circulating VEGF levels were reduced on day +14 regardless of blockade of VEGF. CONCLUSION: Together these findings demonstrate that the allo-reactive responses after allo-HSCT are exaggerated by the blockade of VEGF. VEGF seems to be consumed during the progression of acute GVHD in this murine allo-HSCT model.
Animals ; Body Weight ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Mice ; Oligopeptides ; Peptides ; T-Lymphocyte Subsets ; T-Lymphocytes ; Tissue Donors ; Vascular Endothelial Growth Factor A

Gastric Hodgkin's lymphoma is extremely rare. We present a case of primary Hodgkin's lymphoma arising in the stomach of a 65-year-old woman. The patient complained of epigastric discomfort and reflux for one month. Endoscopic examination revealed a protruding lesion characterized by a smooth surface at the antrum. An abdominal computed tomography uncovered a 2.5 x 2.0 cm, exophytic submucosal mass. After the tentative preoperative diagnosis of a gastrointestinal stromal tumor, a gastric wedge resection was performed. Microscopic examination of the mass demonstrated a diffuse proliferation of large atypical lymphoid cells with mono- and binucleated pleomorphic nuclei and prominent nucleoli. Immunohistochemically, the tumor cells were positive for CD30, CD20, and CD79a, whereas they were negative for cytokeratin, carcinoembryonic antigen, CD3, CD15, epithelial membrane antigen, and anaplastic lymphoma kinase-1. Based on the morphological features and immunohistochemical results, in addition to the clinical findings, a diagnosis of primary gastric Hodgkin's lymphoma was established.
Aged ; Antigens, CD30 ; Carcinoembryonic Antigen ; Female ; Gastrointestinal Stromal Tumors ; Hodgkin Disease ; Humans ; Keratins ; Lymphocytes ; Lymphoma ; Mucin-1 ; Stomach

We report here on a case of invasive ductal carcinoma arising in a recurrent malignant phyllodes tumor. The patient was a 33-year-old woman who presented with a left breast mass, and an excision was then performed. The mass, measuring 7.0 x 4.0 cm in size, was relatively well demarcated with a nodular contour and showed pale gray and solid cut surface with clefts on it. Histologically, the mass mainly consisted of stromal components that were characterized by high cellularity, marked nuclear atypism and brisk mitosis. The sparse glandular components were leaf-like in shape and lined by bland ductal epithelium without any nuclear atypism. Sixteen months later, the patient revisited our hospital with a recurrent mass, and underwent total mastectomy. The recurrent mass contained foci of definite invasive ductal carcinoma in the background of malignant phyllodes tumor, which was identical to the primary mass. This case demonstrates that it is possible that an invasive ductal carcinoma might arise within, at least with, a recurrent malignant phyllodes tumor.
Adult ; Breast ; Carcinoma, Ductal* ; Epithelium ; Female ; Humans ; Mastectomy, Simple ; Mitosis ; Phyllodes Tumor*