Background Thymosin β4 is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin β4 expression in human colorectal cancers (CRCs).
Methods We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β4 expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series.
Results High expression of thymosin β4 was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β4 showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β4 and HIF-1α were overexpressed and that thymosin β4 expression increased in parallel with HIF-1α expression in CRC.
Conclusions A high expression level of thymosin β4 indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β4 is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.
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Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis Joanna I. Lachowicz, Giusi Pichiri, Marco Piludu, Sara Fais, Germano Orrù, Terenzio Congiu, Monica Piras, Gavino Faa, Daniela Fanni, Gabriele Dalla Torre, Xabier Lopez, Kousik Chandra, Kacper Szczepski, Lukasz Jaremko, Mitra Ghosh, Abdul-Hamid Emwas, Mass International Journal of Molecular Sciences.2022; 23(1): 551. CrossRef
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Background There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings.
Methods We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma.
Results From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings.
Conclusions Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.
Colonic muco-submucosal elongated polyp (CMSEP), a newly categorized non-neoplastic colorectal polyp, is a pedunculated and elongated polyp composed of normal mucosal and submucosal layers without any proper muscle layer. We herein report a giant variant of CMSEP associated with intussusception in the rectosigmoid colon, with a review of the literature. A 48-year-old woman underwent a laparoscopic low anterior resection due to multiple large submucosal polypoid masses associated with intussusception. Grossly, the colonic masses were multiple pedunculated polyps with a long stalk and branches ranging in size from a few millimeters to 14.0 cm in length. Microscopically, there was no evidence of hyperplasia, atypia, or active inflammation in the mucosa. The submucosal layers were composed of edematous and fibrotic stroma with fat tissue, dilated vessels, and lymphoid follicles.
Jejunal intussusception and perforation due to enteric muco-submucosal elongated polyp: a case report and literature review Ryosuke Kikuchi, Shigenobu Emoto, Hiroaki Nozawa, Kazuhito Sasaki, Koji Murono, Shinya Abe, Hirofumi Sonoda, Aya Shinozaki-Ushiku, Soichiro Ishihara Surgical Case Reports.2023;[Epub] CrossRef
A stalk with no polyp—A muco‐submucosal elongated polyp in the duodenum Neil O’Morain, Ciaran McCloskey, Sinead Flanagan, Glen Doherty United European Gastroenterology Journal.2023; 11(4): 392. CrossRef
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BACKGROUND Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs). METHODS Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated. RESULTS CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05).
CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis. CONCLUSIONS Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.
We report a case of Langerhans cell sarcoma presented as a solitary mass in the left supraclavicular area in a 31-year-old woman. Computed tomography revealed a relatively well-defined and lightly enhancing mass in the left supraclavicular area, measuring 5.5x4.5x3.2 cm. Excision was subsequently performed. Microscopically, the specimen consisted of an enlarged and partially effaced lymph node.
Nests of different size composed of atypical tumor cells were located in the paracortex and the medulla of the lymph node. The tumor cells exhibited abundant eosinophilic or clear cytoplasm and displayed marked nuclear atypia and increased mitotic figures. Infiltration of many eosinophils was identified in the periphery and between the tumor cells.
The tumor cells were reactive for CD1a and S100 protein.
Ultrastructually, they were found to have Birbeck granules in the cytoplasm.
BACKGROUND Polycystic ovary syndrome (PCOS) is the most common endocrinopathy causing anovulation in women of childbearing age. It has been well established that estrogen receptor-alpha knockout (ERalphaKO) mice display several pathologic ovarian phenotypes of PCOS. The aims of this study were to determine ovarian pathology in new ERalphaKO mice using a CreloxP approach and intra-ovarian ERalpha function as regulating key aspects of PCOS. METHODS ERalphaKO mice, which were deficient in exon 3 of the ERalpha gene, were used. Immunohistochemical studies were done on ovaries of control and ERalphaKO mice using antibodies specific to ERalpha, ERbeta, inhibin-alpha, and alpha-smooth muscle actin (SMA), as well as histochemical staining using Sudan black-B. RESULTS All ovaries of ERalphaKO mice were larger than control mouse ovaries and displayed a disrupted theca-interstitial tissue organization, multiple atretic follicles and multiple hemorrhagic cysts. None of the ERalphaKO mouse ovaries showed a corpus luteum. In addition, heavy deposition of Sudan black-B positive foamy cells was seen. The theca externa of preantral immature follicles and hemorrhagic cysts showed strong expression of alpha-SMA. CONCLUSIONS ERalphaKO mice show hemorrhagic polycystic ovaries and hyperplasia of the theca externa. This study demonstrates that the ERalpha is the functional key to the pathogenesis of PCOS.
Synovial sarcoma is a rare renal neoplasm that is not easy to diagnose unless SYT-SSX fusion transcripts are identified. We report here on a case of primary renal synovial sarcoma in a 35-year-old woman. A mass was discovered by accident in the lower part of the right kidney when ultrasonography was performed, and it was removed via radical nephrectomy. Grossly, the tumor was a homogeneously tan-brown soft mass that measured 4.5x3.2x3.0 cm, and it was encircled by a well-defined cystic space. The lesion exhibited hypercellularity of the oval or short spindle cells that were arranged in various solid sheets or intersecting fascicles. Immunohistochemically, the tumor showed diffuse positivity for vimentin, bcl-2 and CD99, and it showed focal positivity for epithelial membrane antigen.
The SYT-SSX fusion transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR). Synovial sarcoma should be considered in the differential diagnosis when a spindle cell neoplasm is encountered in the kidney.
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Primary Renal Synovial Sarcoma and Clinical and Pathological Findings: a Systematic Review Leandro Blas, Javier Roberti Current Urology Reports.2021;[Epub] CrossRef
In this study, the prevalence of Hepatitis B virus(HBV) DNA in the needle biopsied paraffin embedded liver tissues of chronic hepatitis B patients by rapid nested PCR was examined. DNA was extracted by NaOH with boiling, and amplified by rapid air thermocycler with glass capillary tubes and nested PCR with two primer sets specific for the surface and the core genes of HBV. The PCR results were compared to that of serum HBeAg, serum HBV DNA by dot blot hybridization with a radioactive DNA probe, and tissue immunohistochemical (HBsAg/ HBcAg) studies. Among 44 patients with chronic hepatitis with serum HBsAg positivity, HBV DNA could be detected by PCR in 43 liver tissues (98%).
This results were comparable to the positive rates of 94%(31/33) for serum HBV DNA, 80%(35/44) for serum HBeAg, and 59%(26/44) and 75%(33/44) for tissue HBsAg and HBcAg, respectively. The accordance rate between tissue PCR and serum DNA probe testing was 91%. The results indicate that HBV DNA detection by rapid nested PCR of paraffin embedded liver tissues by needle biopsy is a more sensitive method to detect the HBV DNA carrier than the serum HBeAg or tissue HBsAg/HBcAg status, and is well correlated with the result of serum HBV DNA probe testing. Therefore this method is a practical indicator for the diagnosis and replication status in retrospective analysis.
Carcinoid tumors of the appendix are common incidental findings, but appendiceal tumors with histologic features of both carcinoids and adenocarcinomas are rare, and their biologic behavior and histogenesis are still unclear. We report a case of goblet cell carcinoid of the appendix in a 54-year-old male, who exhibited pain in the right lower abdomen. Microscopically, the tumor contained smooth-bordered, widely separated nests composed of tumor cells with abundant mucin. The principal tumor cell type had a close resemblance to the normal goblet cell.
Histochemically, the tumor cells revealed positive reaction for PAS and alcian blue stain. Immunohistochemically, the tumor showed strong reactivity for carcinoembryonic antigen, chromogranin and, neuron specific enolase but none for cytokeratin and epithelial membrane antigen.
Menetrier's disease is characterized by enlarged gastric folds with foveolar hyperplasia and cystic dilatation of gastric glands. The additional biochemical features of hypoproteinemia, hypochlorhydria, and increased gastric mucus are often encountered. The pathogenesis and etiologic factors have not been clearly defined. In this report, we present two cases of Menetrier's disease in the stomach, one occurring in a 38-year-old male, associated with massive hematemesis, and the other in a 39-year-old male. Grossly, both cases showed marked giant gastric rugal folds resembling cerebral convolutions, sparing the antral portion. Microscopically, the giant gastric rugal folds consisted of the striking foveolar hyperplasia accompanied by an occasional presence of the smooth muscle fibers from the muscularis mucosa. The immunohistochemical stain revealed an intense positive reaction for transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGF-R) in the majority of mucous cells throughout the gastric mucosa and parietal cells, but did not reveal for epidermal growth factor (EGF). We suggested that TGF-alpha and EGF-R might be involved in the pathogenesis of Menetrier's disese.
Recent investigations have revealed that autocrine growth factors and their receptors are closely related and play an important role in controlling cancer cell growth. We performed an immunohistochemical study on the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R), c-erbB-2, and PCNA labelling index in 60 cases of human gastric carcinomas. TGF-alpha was detected in 38 cases (63.3%), EGF in 26 cases (43.3%), EGF-R in 44 cases (73.3%), and c-erbB-2 in 18 cases (30%). These growth factors, EGF-R and c-erbB-2, were found more often in advanced gastric cancers. The PCNA labeling index was significantly higher in tumors with the expression of EGF-R or c-erbB-2. Tumors with simultaneous expression of EGF, TGF-alpha, EGF-R and c-erbB-2 was associated with a high PCNA labeling index. A correlation was observed between the synchronous expression of growth factors and its receptors and histological differentiation. The results suggest that the expression of EGF, TGF-alpha, EGF-R and c-erbB-2 are closely related and plays an important role in the growth and progression of human gastric carcinoma.
Renal dysplasia results from aberrant metanephric histogenesis caused fundamentally by a defect in inducer tissue or responding tissue. Dysplastic kidneys vary tremendously in gross and microscopic appearance but are characterized by abnormal organization and a mixed population of primitive structures, such as fetal or immature cartilage, dysplastic ducts, immature tubules, and undifferentiated mesenchyme. We report a case of unilateral multicystic renal dysplasia associated with an ipsilateral ectopic ureteral orifice entering a seminal vesicle cyst in a 33-year-old man. He was admitted due to primary infertility which had developed three years ago. The his semen analysis revealed oligospermia. No evidence of a family history of renal dysplasia was reported.
Microscopic examination showed that the entire kidney was composed of cysts lined by flattened cells, dysplastic ducts and immature tubules surrounded by collars of spindle cells, primitive mesenchyme, and a few aberrantly formed glomeruli.
We report two cases of hyalinizing trabecular carcinoma (HTC) of the thyroid gland. These two patients were euthyroid women aged 36 and 65 years of age. The tumors were encapsulated and measured 0.8 and 4.0 cm in diameter, respectively.
Histologically, the tumors were composed of a compact proliferation of cells in a lobular and trabecular pattern with an intervening hyalinized, fibrotic vascular stroma. Occasionally the cells were arrayed in microfollicles. Multiple and serial sections showed cords of tumor cells invading into the capsule in both cases and vascular invasion in one case. These findings suggested that HTCs are a malignant counterpart of hyalinizing trabecular adenoma, similar to conventional follicular tumor. Positive immunostaining of tumor cells for thyroglobulin and negative staining for high molecular weight cytokeratin, cytokeratin 19, neuron specific enolase, chromogranin, and synaptophysin allowed distinction from medullary carcinoma. Even though HTCs are an heterogeneous group of tumors, the present two cases are probably variants of follicular carcinoma rather than papillary carcinoma.
Adenoid basal cell tumor of the prostate is a rare tumorous lesion that can be misdiagnosed as adenocarcinoma of the prostate. The malignant potential of adenoid basal cell tumor remains uncertain due to small number of reported cases. This 66-year-old man presented with symptoms of urinary tract obstruction. Under the impression of benign prostatic hyperplasia, a transurethral resection of the prostate (TURP) was performed. The patient was alive with no evidence of recurrence or metastasis 15 months after TURP.
Microscopically, most of the lesions were composed of nodular collections of small nests of basaloid cells with peripheral palisading, and clusters of tumor cells forming cribriform pattern. Multiple areas of basal cell hyperplasia and atypical basal cell hyperpalsia were also observed. The coexistence of basal cell hyperplasia, atypical basal cell hyperpalsia, and adenoid basal cell tumor with cribriform pattern in this case supports a morphologic continuum from the benign hyperplastic lesion to malignant neoplasia.
S100A6 (calcyclin) is a member of the S100 family and has been originally isolated from the cDNA library of Syrian baby hamster kidney cells. The S100A6 gene expression is reported to remain high throughout the cell cycle following induction by serum or growth factors, suggesting that the gene may be required for cell cycle progression. Nevertheless, the role that S100A6 may play in tumor progression remains unknown. In this study, we have explored the expression patterns of S100A6 gene in human thyroid tissues by northern blot analysis. Using the S100A6 monoclonal antibody, we carried out the immunohistochemical staining to determine the distribution/localization of S100A6 protein within tumor or non-tumorous cells of the thyroid. To modulate the regulation of endogenously expressed S100A6 protein in the intracellular level, overexpressed or anti-sense treated transfectant was constructed by using the eukaryotic expression vector. As a result, immunohistochemistry for S100A6 showed a strong positivity in the malignant tumors of thyroid and a high expression level of S100A6 protein affected cell proliferation in the overexpressed transfectant. These findings suggest that S100A6 may be involved in the tumor pathogenesis and provides another parameter for the differentiation of malignant and benign lesions. A well defined monoclonal antibody against S100A6 protein is now available for the immunohistochemical studies of the various thyroid tissues.