Aggressive Malignant Potential Research Articles

Endometrioid Carcinoma of the Uterine Corpus With a Micropapillary Component: A Novel Prognostic Factor For Metastasis.

Micropapillary pattern is a morphologically distinctive form of carcinoma composed of small, hollow, or morula-like clusters of cancer cells surrounded by clear stromal spaces. The neoplastic cells characteristically display a reverse polarity, also known as an ''inside-out'' growth pattern, that is linked to higher frequencies of lymphovascular invasion and lymph nodal metastasis. To the best of our knowledge, it has not been previously recognized in uterine corpus. We report 2 cases of endometrioid carcinoma of the uterine corpus with a micropapillary component. In these cases, histological examination identified an endometrioid carcinoma that had invaded the myometrial layer. The carcinoma cells that constructed the micropapillary components were immunohistochemically positive for EMA. They lined the stromal facing surface of the cell membrane, confirming the inside-out growth pattern, and D2-40 immunohistochemistry confirmed lymphovascular invasion of carcinoma cells. We believe that the micropapillary pattern linked to higher frequencies of lymphovascular invasion and lymph nodal metastasis may be one of the most important invasive patterns in endometrioid carcinomas of the uterine corpus for predicting aggressive malignant potential, prognosis, and recurrence, although further, larger studies are required to evaluate its clinical significance.

Outcomes after Definitive Treatment for Cutaneous Angiosarcomas of the Face and Scalp: Re-Evaluating the Role of Combined Modality Treatment

<h3>Purpose/Objective(s)</h3> Cutaneous angiosarcomas of the face and scalp are rare soft tissue tumors with locally aggressive malignant potential. Previous studies have shown that combined modality treatment (CMT) of surgical resection and adjuvant radiation therapy (RT) improves outcomes. We sought to update our experience with long-term outcomes in patients with cutaneous angiosarcoma of the face and scalp treated with definitive intent. <h3>Materials/Methods</h3> We performed a retrospective review of patients treated at a tertiary cancer center for non-metastatic cutaneous angiosarcoma of the face and scalp between 1962 and 2019, with a majority (69%) since 2000. All patients received definitive local treatment either with surgery, RT, or CMT. The Kaplan-Meier method was used to estimate actuarial overall survival (OS), disease-specific survival (DSS) and local control (LC). Multivariable analyses were conducted using Cox proportional hazards model. <h3>Results</h3> Median follow-up for all patients was 33 months. Of the 143 patients, the majority were male (n=109, 76%) and had a primary lesion on the scalp (n=87, 61%). Median age was 70 years at diagnosis (IQR 64-76). Slightly less than half (n=59, 41%) of patients had multifocal disease at diagnosis, and 20 (14%) presented with nodal involvement. CMT was the most common treatment approach (n=69, 48%), followed by RT alone (n=50, 35%) and surgery alone (n=24, 17%). Forty-three percent of patients (n=61) had a local relapse, resulting in a 5-yr LC of 51%. On univariable analysis 5-yr LC was significantly worse in patients with tumors >5 cm at diagnosis (19% vs 59% <5cm, p=0.01), those with multifocal disease at presentation (35% vs 59% unifocal, p<0.005), and those treated with single modality therapy (SMT) (29% vs 75% CMT, p<0.005). These factors all remained significantly associated with poorer LC on multivariable analysis (>5cm HR 2.30 [1.27-4.16], multifocal disease HR 1.95 [1.10-3.43], SMT HR 3.74 [2.01-6.96]). The 5-yr OS and DSS were 45% and 56%, respectively. When evaluating factors associated with DSS, tumor size >5 cm (HR 2.15 [95%CI 1.20-3.88]), multifocal disease at presentation (HR 1.80 [1.02-3.18]), primary site other than the scalp (HR 0.53 [0.29-0.99]), and the use of SMT (HR 2.95 [1.59-5.50]) emerged as independent predictors of DSS. The presence of multifocal disease and large tumor size were also associated with worse OS on both univariate and multivariable analyses (HR 1.59 [1.02-2.50], HR 2.00 [1.21-3.31], respectively). The use of chemotherapy was not associated with any outcome. <h3>Conclusion</h3> Large tumor size (>5 cm) and the presence of multifocal disease are negative prognostic factors in patients presenting with cutaneous head and neck angiosarcomas. With longer follow-up, our data continues to suggest that primary local therapy consisting of CMT improves LC and DSS outcomes for these patients and should remain standard of care when feasible.

Educational and Psychological Support Combined with Minimally Invasive Surgical Technique Reduces Perioperative Depression and Anxiety in Patients with Bladder Cancer Undergoing Radical Cystectomy.

Radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is an extensive and morbid operation, often associated with permanent alteration of body image and disability. Combined with the aggressive malignant potential of MIBC and considerable risk of complications, it poses a serious threat to the psychological well-being of patients. Educational deficiencies causing uncertainty and confusion aggravate surgery-related anxiety and may lead to depression along with further social disability. We conceived a preoperative supportive program named “Cystocare” held by urologists, psychologists, stoma therapists and cancer survivors to facilitate patients’ adaptation and coping. We aimed to evaluate whether participation in Cystocare meetings would alleviate emotional distress in patients undergoing RC. We included 95 consecutive patients who filled Hospital Anxiety and Depression Score questionnaires before RC and on discharge. The intervention arm (A) comprised 32 Cystocare participants. The remaining 63 patients who received standard preparation constituted the control arm (B). Whilst there were no differences in median anxiety and depression scores preoperatively, in postoperative measurement, the intervention arm showed a lower median depression score than controls: 3 vs. 8 points, p = 0.015. On multivariate analysis we confirmed lower risk of postoperative depression in Cystocare participants: OR = 0.215 (95%CI: 0.066–0.699), p = 0.011, along with lower odds of preoperative anxiety in patients undergoing laparoscopic RC: OR = 0.365 (95%CI: 0.136–0.978), p = 0.045, and higher risk of prolonged hospital stay in patients experiencing postoperative anxiety OR = 17.114 (95%CI: 1.283–228.234) p = 0.032. Preoperative educational and supportive intervention complements laparoscopic RC in the alleviation of surgery-related anxiety and depression. The support group meetings provide an attractive and cost-effective opportunity to moderate emotional response in patients undergoing RC, and as such, deserve widespread adoption.

Mixed histology poses a greater risk for noncurative endoscopic resection in early gastric cancers regardless of the predominant histologic types.

Clinicopathologic characteristics and treatment outcomes of mixed-histological-type (MT) early gastric cancers (EGCs) treated with endoscopic submucosal dissection (ESD) have not been sufficiently elucidated. We aimed to clarify them in comparison with pure-histological-type EGCs. We used 3022 consecutive EGCs in 2281 patients treated with ESD from our prospectively maintained database. Cases were stratified into four groups according to the final diagnosis of the resected specimen are as follows: 2780 pure differentiated-type (DT), 127 DT-predominant MT (D-MT), 87 pure undifferentiated-type (UDT), and 28 UDT-predominant MT (U-MT). Clinicopathologic characteristics and treatment outcome were compared between pure DT and D-MT, and between pure UDT and U-MT separately. Risk factors for deep submucosal invasion, lymphovascular invasion, and a final diagnosis of MT were identified using multivariate analysis. Both D-MT (41.7 vs. 92.0%; P < 0.0001) and U-MT (35.7 vs. 75.9%; P = 0.0002) showed a significantly lower curative resection rate than their pure histologic counterparts. Multivariate analysis revealed that MT was an independent risk factor for deep submucosal (OR 6.55; 95% CI, 4.18-10.14) and lymphovascular (OR 4.74; 95% CI, 2.72-8.29) invasion. Preoperative biopsy results that did not show well-differentiated tubular adenocarcinoma (OR 28.2; 95% CI, 18.9-42.9) were an independent risk factor for a final diagnosis of MT. MT poses a greater risk for noncurative resection regardless of the predominant histologic types, reflecting more aggressive malignant potential. Although a biopsy examination rarely shows MT, clinicians should consider the possibility of MT when a biopsy examination does not show well-differentiated tubular adenocarcinoma.

Morphological Changes in the Cells of the Ductal Adenocarcinoma of the Pancreas at Epithelial-Mesenchymal Transition

The aim of the research was to study the expression of marker genes for the epithelial-mesenchymal transition in the ductal adenocarcinoma of the pancreas.Material and methods. Surgical material from 44 patients with ductal adenocarcinoma of the pancreas was subjected to morphological analysis with molecular genetic research. Total RNA was detected in the detected sections of the anaplastic component using the RNeasy Mini Kit (Qiagen, Germany). 5 marker genes were used for molecular genetic studies of the epithelial-mesenchymal transition (EMT): ZEB1, ZEB2, CDH1, VIM, SNAIL1 (SLUG). Gene expression was measured in triplicate using an EvaGreen intercalating dye. On serial paraffin sections using tissue microarrays technology, immunohistochemical detection of p63, smooth muscle actin, total cytokeratin, cytokeratin 7, vimentin, E-cadherin (Ventana) was performed.Results. As a result of the study, a positive reaction with mesenchymal markers (vimentin, p63, smooth muscle actin) was detected in the cells of the anaplastic component, in contrast to the glandular component. In a molecular study of the anaplastic component, changes in gene expression were characterized as EMT-positive.Conclusion. The heterogeneity of ductal cancer is manifested in the appearance of an anaplastic (sarcomalike) component, in which the ability of epithelial tumor cells to acquire the property of mesenchymal cells that do not require stroma and have aggressive malignant potential that affects the survival of patients is traced.

PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer

ObjectivesPD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) plays important roles in regulating the antitumor T cell response. However, the mechanistic and clinical significance of the effect of PD-L1 on TCs versus ICs remains unclear. On the other hand, tumor-associated macrophages (TAMs), M2 macrophages in particular, can promote tumor progression. MethodsWe evaluated PD-L1 expression on TCs and ICs using Ventana SP263 assay and the stromal M2 TAM distribution using CD163 staining in 160 consecutive patients with resected non-small cell lung cancer (NSCLC). ResultsPD-L1 expression on TCs and ICs was significantly higher in stromal M2 TAM-high group than in stromal M2 TAM-low group (p < 0.001 and p < 0.001, respectively). Regarding the clinical significance of PD-L1, PD-L1 expression on TCs was significantly associated with histology (p = 0.001), tumor differentiation (p < 0.001) and nodal status (p = 0.029). Furthermore, PD-L1 expression on ICs was significantly associated with histology (p < 0.001), tumor differentiation (p < 0.001), tumor status (p = 0.024), nodal status (p = 0.016), and pathologic stage (p = 0.004). The disease-free survival rate was significantly lower in patients with PD-L1-positive TC than in those with PD-L1-negative TC (p = 0.023), as well as in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p < 0.001). Furthermore, the overall survival rate was significantly lower in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p = 0.023). ConclusionsDuring tumor progression in NSCLC, the presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs. In patients with NSCLC, PD-L1 expression both on TCs and ICs was associated with malignant behaviors, which was more in case of ICs.

Immunohistochemical evaluation of inducible nitric oxide synthase in the epithelial lining of odontogenic cysts: A qualitative and quantitative analysis.

Introduction:The three common odontogenic cysts include radicular cysts (RCs), dentigerous cysts (DCs), and odontogenic keratocysts (OKCs). Among these 3 cysts, OKC is recently been classified as benign keratocystic odontogenic tumor attributing to its aggressive behavior, recurrence rate, and malignant potential. The present study involved qualitative and quantitative analysis of inducible nitric oxide synthase (iNOS) expression in epithelial lining of RCs, DCs, and OKCs, compare iNOS expression in epithelial linings of all the 3 cysts and determined overexpression of iNOS in OKCs which might contribute to its aggressive behavior and malignant potential.Aims:The present study is to investigate the role of iNOS in the pathogenesis of OKCs, DCs, and RCs by evaluating the iNOS expression in the epithelial lining of these cysts.Subjects and Methods:Analysis of iNOS expression in epithelial lining cells of 20 RCs, 20 DCs, and 20 OKCs using immunohistochemistry done.Statistical Analysis Used:The percentage of positive cells and intensity of stain was assessed and compared among all the 3 cysts using contingency coefficient. Kappa statistics for the two observers were computed for finding interobserver agreement.Results:The percentage of iNOS-positive cells was found to be remarkably high in OKCs (12/20) –57.1% as compared to RCs (6/20) – 28.6% and DCs (3/20) – 14.3%. The interobserver agreement for iNOS-positive percentage cells was arrived with kappa values with OKCs → Statistically significant (P > 0.000), RCs → statistically significant (P > 0.001) with no significant values for DCs. No statistical difference exists among 3 study samples in regard to the intensity of staining with iNOS.Conclusions:Increased iNOS expression in OKCs may contribute to bone resorption and accumulation of wild-type p53, hence, making OKCs more aggressive.

Cisplatin-resistant osteosarcoma cells possess cancer stem cell properties in a mouse model.

Osteosarcoma is the most common malignancy of the bones, and although advances in chemotherapy and surgery had been achieved in recent years, the long-term survival rate has reached a plateau. The main reason for this is the aggressive malignant potential and poor response of the disease to chemotherapy. However, several studies have found that tumor resistance is associated with cancer stem cells (CSCs). To address this issue, in the present study, osteosarcoma cells were treated with specially designated concentrations of cisplatin (CDDP) in a mouse model. Hematoxylin and eosin staining analyses were performed to assess tissue structure, in vivo passaging and CDDP treatment. Drug resistance genes and well-established stemness genes were detected by quantitative polymerase chain reaction. A serum-starved sphere formation assay was adopted to evaluate the ability to generate spherical clones and flow cytometry as used to test the expression of the cluster of differentiation 117 and Stro-1 surface markers, known as markers of CSCs. It was found that CDDP could induce an effect of resistance in the osteosarcoma cells, which possessed cancer stem CSC properties, as shown by the elevated expression of CSC marker genes and the higher expression of the cluster of differentiation 117 and Stro-1 surface markers. Moreover, the cells that dissociated from the tumor tissues exhibited an increased ability to form sarcospheres. The results of this study provided a significant correlation between resistance and CSCs, and revealed a clue indicating that osteosarcoma recurrence is likely to be associated with CSCs.

Intracellular Elemental Patterns of Apoptosis Resistance in Transdifferentiated Androgen-Dependent Prostatic Carcinoma Cells.

The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PC) cells relates to tumor progression and hormone resistance. PC cells may survive and function in androgen-deprived environments, where they could establish paracrine signaling networks, providing stimuli for the propagation of local carcinoma cells. We previously demonstrated, using electron probe X-ray microanalysis (EPXMA), in LNCaP, PC-3, and Du 145 cell lines that apoptosis is associated with intracellular elemental changes, and that the NE secretory products, bombesin and calcitonin, inhibit etoposide-induced apoptosis, as well as some of these elemental changes. In this study, LNCaP cells were induced in vitro to transdifferentiate under androgen deprivation, to mimic the role of NE cells in the apoptotic activity of transdifferentiated androgen-dependent PC cells. Changes in intracellular ion content associated with apoptosis, assessed by EPXMA, demonstrate that the transdifferentiated LNCaP cells are resistant to etoposide-induced apoptosis and also to the etoposide-induced elemental changes. The aggressive malignant potential of PC with neuroendocrine differentiation, associated with hormonal independence, is partly because of the ability that most NE tumor cells have to escape apoptosis, which can enhance the malignant properties of tumor cells and may have therapeutic implications as tumor cells are usually resistant to cytotoxic drugs as etoposide.

The role of endoscopic ultrasound in pancreatic cancer screening.

Pancreatic cancer (PC) is a highly lethal cancer. Despite a significant advancement in cancer treatment, the mortality rate of PC is nearly identical to the incidence rates. Early detection of tumor or its precursor lesions with dysplasia may be the most effective approach to improve survival. Screening strategies should include identification of the population at high risk of developing PC, and an intense application of screening tools with adequate sensitivity to detect PC at an early curable stage. Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) seem to be the most promising modalities for PC screening based on the data so far. EUS had an additional advantage over MRI by being able to obtain tissue sample during the same examination. Several questions remain unanswered at this time regarding the age to begin screening, frequency of screening, management of asymptomatic pancreatic lesions detected on screening, timing of resection, and extent of surgery and impact of screening on survival. Novel techniques such as needle-based confocal laser endomicroscopy (nCLE), along with biomarkers, may be helpful to identify pancreatic lesions with more aggressive malignant potential. Further studies will hopefully lead to the development of strategies combining EUS with other technological/biological advancements that will be cost-effective and have an impact on survival.

Core 2 β-1, 6-N-acetylglucosaminyltransferase-1 expression in prostate biopsy specimen is an indicator of prostate cancer aggressiveness

IntroductionTo avoid over-treatment of early stage prostate cancer (PCa), predictive biomarkers for PCa aggressiveness which can be obtained during pre-treatment evaluation are essential. Core 2 β-1, 6-N-acetylglucosaminyl-transferase-1 (GCNT1) is a key enzyme that forms core 2 branched O-glycans, the expression of which is associated with aggressive potential of prostate cancer. We examined whether GCNT1 expression in prostate biopsy specimen can predict cancer recurrence after radical prostatectomy for the patients with with PCa. We then investigated molecular background for aggressive malignant potential mediated by GCNT1 expression. MethodsParaffin-embedded PCa biopsy specimens were immunohisto-chemically tested for GCNT1 expression using an anti-GCNT1 monoclonal antibody. We also examined the role of GCNT1 in PCa progression using cell lines which express high or low levels of GCNT1. ResultsGCNT1 expression correlated with D′ Amico's recurrence risk classification. The GCNT1-positive rate in organ confined PCa was significantly lower than that in PCa with extra-prostatic extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that GCNT1 expression status was an independent risk factor for PSA recurrence after radical prostatectomy. Subsequent basic study revealed that GCNT1-over-expressing cells produced a significantly larger amount of growth factors when co-cultured with prostate stromal cells compared with GCNT1-knocked down cells and formed larger tumors. ConclusionsGCNT1 expression in prostate biopsy specimen is a significant and independent predictor of recurrence after radical prostatectomy, which can be used in pre-treatment decision making for the patient. Further validation study is necessary to establish clinical implication of GCNT1 in management of PCa.

Thymic neuroendocrine tumor in a patient with multiple endocrine neoplasia type I : The limitations of surveillance

Multiple endocrine neoplasia type I (MEN1) is an autosomal dominant disorder associated with pituitary and parathyroid adenomas and neuroendocrine tumors (NETs) of the pancreas. Pancreatic NETs, most of which are non-functional, are now the primary life-threatening manifestation of MEN1. Some patients with this disorder develop NETs of the thymus, which are typically characterized by aggressive behavior and malignant potential. Although rare in the general population, 25% of all reported thymic NETs have occurred in patients with MEN1. With the aid of advancements in imaging and biomarkers, the clinician is now better equipped in detecting NETs in this high-risk group. In this report, we present a patient whose incidentally discovered thymic NET led to the diagnosis of MEN1. We provide an overview of MEN1-associated NETs with a specific focus on the use of chromogranin A (CgA) in disease surveillance.

Multiple carcinosarcomas of the kidney: A case report and review of the literature.

Carcinosarcomas are biphasic tumors comprising epithelial and mesenchymal components. Primary carcinosarcoma of the kidney is extremely uncommon and accounts for <1% of all malignant renal tumors. Primary carcinosarcoma of the kidney generally occurs after the age of 60 and the majority of the patients are men. This is the case report of a 56-year-old male patient who presented with left flank pain. Ultrasonography and computed tomography (CT) revealed ureterohydronephrosis and a left distal ureteral stone (25 mm). Renal scan with diethylenetriamine pentaacetate and dimercaptosuccinic acid revealed a non-functional kidney and a left nephroureterectomy was performed. The pathological examination of the surgical specimen revealed high-grade multiple carcinosarcomas according to the Union for International Cancer Control and cancer staging according to the tumor-node-metastasis classification determined the disease as stage T3aN0M0. At 6 months, the patient was administered systemic adjuvant chemotherapy (CTx) due to widespread lung and liver metastases on 18F-fluorodeoxyglucose positron-emission tomography/CT. However, no response was achieved with systemic CTx. The precise histogenesis of this type of cancer has not been determined. Carcinosarcoma of the kidney is a biphasic tumor and its biphasic nature must be confirmed using immunohistochemical methods during pathological diagnosis. The mesenchymal components of sarcomatoid carcinomas must be verified by pathological examination. Metaplastic changes may have malignant potential but should not be considered as malignant lesions. The most significant histopathological parameter that supports the diagnosis of sarcomatoid carcinoma is the identification of transitional zones between the epithelial and mesenchymal cells. Carcinosarcoma is characterized by aggressive malignant potential and a poor prognosis. An effective curative method has not yet been established, with the exception of radical surgery. It is therefore recommended to perform efficient surgical excision with adequate surgical margins.

Penile cancer

Penile cancer is a rare disease with aggressive malignant potential. Organ-preserving methods of treatment are feasible at earlier stages; hence the prompt diagnostics and staging of the tumor spread are mandatory. The review of recent literature in penile cancer is presented; a case report from the authors’ clinical practice is used to discuss the approach to patients’ diagnostics and treatment.

Epithelial tumours of the lacrimal gland: a clinical, histopathological, surgical and oncological survey

Epithelial tumours of the lacrimal gland represent a large spectrum of lesions with similarities in clinical signs and symptoms but with different biological behaviour and prognosis. They are rare, but with aggressive malignant potential. Tumours of the lacrimal gland may present with swelling of the lacrimal gland, displacement of the eyeball, reduced eye motility and diplopia. Pain and symptoms of short duration before the first ophthalmic consultation are characteristic of malignant tumours. The histological diagnosis determines the subsequent treatment regimen and provides important clues regarding the prognosis. The purpose of this paper is to describe the various primary epithelial tumours of the lacrimal gland. In the first part of the review, the frequency, demographics, clinical presentation and diagnostic features are described. In the second part, primarily tumour-specific histological characteristics are given. Finally, treatment modalities including surgical procedures and medical oncology as well as prognosis are discussed.

Solitary skin metastasis from sarcomatoid carcinoma of the bladder: a case report

IntroductionCutaneous metastases from carcinomas of the bladder are very rare. They are related to advanced stages of the disease and have poor prognosis with low survival rates. The common treatment modality of cutaneous metastases from a primary bladder cancer is wide local excision followed by chemotherapy.Case presentationWe report a case of solitary skin metastasis from a rare type of urinary bladder carcinoma in a 68 year-old Caucasian man. Urinary bladder carcinoma metastasizing to the skin is an uncommon finding despite the high incidence of this tumor. Skin metastasis generally presents in the late stages of this disease and indicates a poor outcome.ConclusionsBecause of the extremely aggressive malignant potential of sarcomatoid carcinomas, the indications for a transurethral resection of the bladder should be carefully assessed and suitable therapeutic strategies should be examined further.

Identifying Circulating Tumor Stem Cells That Matter: The Key to Prognostication and Therapeutic Targeting

TO THEEDITOR: We read with interest the article by Iinuma et al 1 that describes their study examining the clinical significance of cancer stem cells in the peripheral blood of patients with colorectal cancer (CRC). The defining characteristics of a circulating cancer stem cell (CTSC) are its capacity for self-renewal and for initiation of distant metastases; some of these cells are also resistant to traditional chemo- therapy. 2,3 The concept that circulating tumor stem cells can be iden- tified and targeted is attractive and has major diagnostic, prognostic, and therapeutic implications for patients with metastatic cancer. However, the identification of authentic CTSCs continues to be a challenge because of the lack of a clear understanding of the biologic heterogeneity of tumor stem-cell populations and also because of the lack of characterization of surface markers that predict clinically im- portant subsets of CTSCs, such as those with aggressive malignant potential or drug resistance.

Small invasive colon cancer with systemic metastasis: A case report

BackgroundRecently, especially in Japan, several researchers have suggested that colorectal cancer can develop not only through an adenoma-carcinoma sequence but also from normal mucosa via a de novo pathway, and that these de novo cancers have more aggressive malignant potential. We report a case of aggressive colon cancer resulting in systemic metastasis despite small tumour size.Case PresentationA 35-year-old woman presented at the referring hospital with swelling of the left cervical lymph node. Biopsy of the lymph node revealed metastatic adenocarcinoma; however, CT scan and mammography were unable to identify the site of the primary lesion. She was diagnosed with unknown primary cancer and referred to our hospital for further examination. Immunohistochemical reevaluation showed the cervical lymph node biopsy specimen to be positive for CDX2 and CK20 and negative for CK7 expression, leading us to suspect the presence of a primary colorectal cancer. We performed a total colonoscopy, and detected a small protruding lesion in the transverse colon. The tumour was only 12 mm in diameter, with a central depressed component and a severely thickened stalk, which suggested direct cancer invasion of the deep submucosa. We concluded that this lesion was the site of origin of the metastasis despite the small tumour size, and performed diagnostic endoscopic mucosal resection. The lesion was found to have an intramucosal cancer component, demonstrating that this lesion represented primary colon cancer. The patient was referred to the gastrointestinal oncology division for systemic chemotherapy.ConclusionsIn this case, immunohistochemical findings strongly suggested the existence of a colorectal cancer. The non-polypoid gross appearance of the tumour suggested that it can originate de novo , thus providing a valuable case in support of the aggressive malignant potential of a de novo colorectal cancer pathway.

An Oncogenic Role for the Phosphorylated h-Subunit of Human Translation Initiation Factor eIF3

Dysregulation of protein synthesis has been implicated in oncogenesis through a mechanism whereby "weak" mRNAs encoding proteins involved in cell proliferation are strongly translated when the protein synthesis apparatus is activated. Previous work has determined that many cancer cells contain high levels of eIF3h, a protein subunit of translation initiation factor eIF3, and overexpression of eIF3h malignantly transforms immortal NIH-3T3 cells. This is a general feature of eIF3h, as high levels also affect translation, proliferation, and a number of malignant phenotypes of CHO-K1 and HeLa cells and, most significantly, of a primary prostate cell line. Furthermore, overexpressed eIF3h inhibits Myc-dependent induction of apoptosis of primary prostate cells. eIF3h appears to function through translation, as the initial appearance of overexpressed eIF3h in rapidly induced NIH-3T3 cells correlates tightly with the stimulation of protein synthesis and the generation of malignant phenotypes. This oncogenic potential of eIF3h is enhanced by phosphorylation at Ser(183). Finally, reduction of eIF3h levels in breast and prostate cancer cell lines by short interfering RNA methods reduces their rates of proliferation and anchorage-independent growth in soft agar. The results provide compelling evidence that high eIF3h levels directly stimulate protein synthesis, resulting in the establishment and maintenance of the malignant state in cells.

膀胱肉腫様癌の1例

A 49-year-old female visited to our department with complaints of gross hematuria and micturition pain. Cystoscopic examination revealed a 5-cm diameter solid broad-based tumor located at the front wall of the bladder. Histologically, the tumor was composed of grade 2 urothelial carcinoma (UC) element and sarcomatous spindle cell element. Immunohistochemical examination demonstrated that both UC and spindle cells were positive for cytokeratin. In addition, spindle cells did not stain for S-100 protein or smooth muscle actin. We diagnosed the tumor as sarcomatoid carcinoma and performed total cystectomy and ileal conduit without chemotherapy and radiation. The patient has remained without any evidence of recurrence for 14 months after operation. Sarcomatoid carcinoma of the bladder has aggressive malignant potential and poor prognosis. An appropriate adjuvant therapy for sarcomatoid carcinoma with metastasis has not been established. Total cystectomy is recommended as soon as possible after pathological diagnosis in the same manner as conventional high grade UC.