Pancreatic Juice Cytology Evaluations Using Synthetic Secretin and Serial Pancreatic Juice Aspiration Cytological Examination for the Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pathological examination by endoscopic ultrasound-fine needle aspiration is not possible in approximately 10% of pancreatic tumor cases. Pancreatic juice cytology (PJC) is considered an alternative diagnostic method. However, its diagnostic capability is insufficient, and PJC has been repeatedly redevised. Serial pancreatic juice aspiration cytological examination (SPACE) and secretin-loaded PJC (S-PJC) have been recently introduced as alternative diagnostic methods. This study aimed to determine the diagnostic capacity and safety of SPACE and S-PJC using a propensity score-matched analysis. The sensitivity, specificity, and accuracy were 75.0%, 100%, and 92.3% for S-PJC, respectively, and 71.4%, 100%, and 92.3% for SPACE, respectively, meaning that there was no significant difference between the groups. Four patients (15.4%) each in the S-PJC and SPACE groups experienced complications, including postendoscopic retrograde cholangiopancreatography, pancreatitis, and cholangitis. Overall, there was no difference in efficacy and safety between the SPACE and S-PJC groups.

Pembrolizumab-induced aseptic meningitis in a patient with non-small cell lung cancer: A case report and literature review of aseptic meningitis as an immune-related adverse event.

Aseptic meningitis is a rare immune-related adverse event (irAE), which occurs during treatment with immune checkpoint inhibitors (ICIs). This condition has non-specific symptoms and exhibits no clear signs on magnetic resonance imaging (MRI). There are only a few reports of aseptic meningitis caused by pembrolizumab treatment for non-small cell lung cancer (NSCLC). The present study includes a report of such a case and a review of the related literature. A 67-year-old Japanese man received first-line pembrolizumab treatment for NSCLC and subsequently developed severe nausea and vomiting. No significant findings were observed following a computed tomography (CT) scan, MRI of the brain and upper gastrointestinal tract, or upper gastrointestinal endoscopy. Cerebrospinal fluid analysis revealed lymphocyte infiltration and elevation of the IgG index, without indications of metastasis or infection, which suggested the presence of aseptic meningitis. The symptoms immediately improved following prednisolone treatment, and aseptic meningitis was diagnosed as an irAE related to pembrolizumab treatment. Given that aseptic meningitis can cause non-specific symptoms, including headache and nausea, the possibility of an irAE should be considered in patients with non-specific symptoms who are receiving ICIs, and a cerebrospinal fluid examination should be performed.

Chronic Active Epstein-Barr Virus Infection Indistinguishable from Autoimmune Hepatitis: A Case Report.

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease, mainly affecting children, typically characterized by persistent infectious mononucleosis (IM)-like symptoms. We describe an adult case of CAEBV without IM-like symptoms, which was indistinguishable from autoimmune hepatitis (AIH). A 60-year-old woman with liver damage was diagnosed with AIH (International Diagnostic Score: 16 points). She had been treated with prednisolone for three years; however, her transaminases had never normalized. She was admitted for another liver biopsy due to repeated high fevers and worsening of her liver damage over two months. Her EBV-DNA copy number was 2.9 × 104 copies/µg DNA, and EBV-encoded small RNA1-positive lymphocytic infiltration was observed in both the present and previously collected (three years ago) liver tissue samples. This case implies that hepatic involvement in a CAEBV without IM-like symptoms is difficult to distinguish from AIH and may be misdiagnosed. In some steroid resistant AIH cases, evaluating for CAEBV may be valuable.

Efficacy and Safety of Pancreatic Juice Cytology with Synthetic Secretin in Diagnosing Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas.

The risk of malignant transformation of intraductal papillary mucinous neoplasm (IPMN) is presently assessed using imaging, which remains unsatisfactory. Given the high viscosity of pancreatic juice, pancreatic juice cytology (PJC) is considered an investigational procedure. We previously demonstrated that the diagnostic performance of PJC was improved via synthetic secretin loading in pancreatic ductal carcinoma. This study aimed to evaluate the efficacy of synthetic secretin-loaded PJC (S-PJC) for IPMN. The usefulness and safety of S-PJC were prospectively evaluated in 133 patients with IPMN. Overall, 92, 12, and 26 patients had branch duct, main duct, and mixed-type lesions, respectively. The risk classifications based on the 2017 international consensus guidelines were high-risk stigmata, worrisome features, and no risk in 29, 59, and 45 patients, respectively. Synthetic secretin loading improved the sensitivity of PJC from 50.0% to 70.8%. Complications included 13 (9.8%) cases of mild pancreatitis, 1 (0.8%) case of acute cholangitis, and 1 (0.8%) case of Mallory-Weiss syndrome, all of which resolved with conservative treatment. In conclusion, synthetic secretin-loaded PJC improved the diagnostic performance of cytology for malignant IPMN. We recommend using synthetic secretin-loaded PJC for the preoperative pathological diagnosis of malignant IPMN in clinical settings.

[Ciliated Muconodular Papillary Tumor of the Lung:Report of a Case].

Ciliated muconodular papillary tumor( CMPT) is a rare true pulmonary tumor consisting of bronchiolar cellular elements. Although this tumor cannot be classified as benign or malignant, it is mostly believed to be a benign bronchiolar adenoma. Recently, CMPT has been divided into two subtypes: proximal and distal. Herein, we report a case of a proximal type of CMPT containing abundant mucus cells in a 70-year-old woman. Thoracoscopic resection of the tumor in the left lower lobe was successfully performed, and the patient has been well without recurrence or metastasis for more than three years after surgery.

Primary Intracranial Neuroendocrine Tumor of the Skull Base Complicated with Tension Pneumocephalus after Radiotherapy.

Neuroendocrine tumors (NETs) are neoplasms that originate from cells of the endocrine and nervous systems, and are commonly found in the gastrointestinal and respiratory tracts. Primary intracranial NETs are extremely rare and have been the focus of only a few studies thus far. Herein, we report the case of a primary intracranial NET of the skull base complicated with tension pneumocephalus after radiotherapy. An 84-year-old woman visited a local hospital for a head injury, and CT revealed a skull base tumor. MRI showed that the tumor was located mainly on the clivus and extended into the paranasal sinuses and nasal cavity. We biopsied the tumor via the nasal cavity, and the pathological diagnosis was NET, WHO grade 2. We subsequently administered focal intensity-modulated radiation therapy, but the patient developed tension pneumocephalus 1 year after radiotherapy. We therefore performed endoscopic transnasal cerebrospinal fluid leak closure with a nasoseptal flap. The postoperative course was successful, and the patient returned home but died of an unknown cause 2 years after discharge. The optimal postoperative management of primary intracranial NETs remains controversial. Tension pneumocephalus related to radiotherapy is a rare complication. Assessing skull bone erosion before radiotherapy and performing regular radiological follow-up examinations are essential to prevent this rare complication.

Juvenile Granulosa Cell Tumor with Elevated Peripheral Interleukin-6 Level Shows Prolonged Fever and Delayed Puberty.

Juvenile granulosa cell tumor (JGCT), classified as a sex cord-stromal tumor, is a rare neoplasm. This is an instructive case report of JGCT accompanied by augmented interleukin (IL)-6 secretion. A 13-year-old girl with prolonged fever and delayed puberty was diagnosed with JGCT of the left ovary based on an imaging study and pathological investigation. Although it was not clear whether IL-6 was secreted from the tumor cells, her serum level of IL-6 was very high. After tumorectomy, the patient's symptoms immediately disappeared, her IL-6 level decreased, and she entered puberty. Therefore, augmented IL-6 secretion production induced by tumors should be considered a potential cause of prolonged fever and/or delayed puberty.

Detection of Disease-specific Fusion Genes of Soft Tissue Tumors Using Formalin-fixed Paraffin-embedded Tissues; Its Diagnostic Usefulness and Factors Affecting the Detection Rates.

BACKGROUND: Recent rapid advances in molecular biology have led the discovery of disease-specific novel fusion genes in a variety of soft tissue tumors. In this study, we attempted to detect these fusion genes using formalin-fixed paraffin-embedded (FFPE) tumor tissues and investigated their clinical utility and factors that affect the results of examination. METHODS: Reverse transcription polymerase chain reaction for the detection of tumor-specific fusion genes was performed using 41 FFPE tumor samples obtained from 37 patients representing nine histological types of soft tissue tumors that were diagnosed from 2006 to 2017 in our laboratory. RESULTS: Fusion genes in 19 (51.3%) out of 37 cases were detected successfully. Relatively high detection rates were observed in synovial sarcomas (100%, 4/4) and alveolar rhabdomyosarcomas (75%, 3/4). The detection rates of fusion genes were inversely correlated with the storage period of FFPE blocks. Decalcification by Plank-Rychlo solution significantly affected detection rates of the internal control gene (P = 0.0038). In contrast, there was no significant difference in detection rates between primary and metastatic lesion, or biopsy and resection material, or presence and absence of treatment history. CONCLUSION: In certain histological types, detection of disease-specific fusion genes of soft tissue tumors using FFPE tissues showed high sensitivity and thus had diagnostic utility. However, due to the diversity of fusion patterns and the low-quality of nucleic acid, the detection rate as a whole was sluggish and required further improvement. For factors affecting the detection results, our results suggested that it was impossible to detect fusion genes by decalcified FFPE tissues, but it may be not necessary to consider factors such as the type of specimen (biopsy or resection) and treatment history of the patients when selecting the FFPE tissues.

Upregulation of glucose and amino acid transporters in micropapillary carcinoma.

Micropapillary carcinoma (MPC), a relatively rare histologic carcinoma observed in various organs, is associated with vascular invasion, nodal metastasis, and poor prognosis. MPC is different from papillary carcinoma as it has no fibrovascular core and is thus considered essentially hypovascular. MPCs are known to upregulate glucose transporter 1 (GLUT1) via the activation of a transcription factor, hypoxia-inducible factor (HIF)-1. Here we evaluated the expression of nutrient transporters in MPCs to gain a better understanding of the system used by MPCs to compensate for their intrinsic poor vascularity. We immunohistochemically evaluated 29 MPCs including breast (n=14), lung (n=8), gastrointestinal tract (n=5), and urinary tract cancers (n=2), and compared them with non-micropapillary control cancers (n=32) regarding the expression of amino acid (ASCT1, ASCT2, LAT1, and SNAT1) and glucose (GLUT1, GLUT2) transporters. Each section was scored by the staining intensity (0-3) multiplied by the occupying area (0-10), with a possible range 0-30. The average scores of the MPC and control groups were compared by Student's or Welch's t-test according to the homoscedasticity. The MPC group showed significantly higher scores for ASCT1 (p=0.007), ASCT2 (p=0.001), GLUT1 (p<0.001), and GLUT2 (p<0.001), whereas no significant scores were noted for LAT1 and SNAT1. In conclusion, MPC could be associated with the upregulation of several nutrient transporters, which may contribute to the malignant potential by supporting the survival of cancer cells.

Merkel cell polyomavirus and Langerhans cell neoplasm.

BACKGROUND: The relationship between various external agents such as pollen, food, and infectious agents and human sensitivity exists and is variable depending upon individual's health conditions. For example, we believe that the pathogenetic potential of the Merkel cell polyomavirus (MCPyV), the resident virus in skin, is variable and depends from the degree of individual's reactivity. MCPyV as well as Epstein-Barr virus, which are normally connected with humans under the form of subclinical infection, are thought to be involved at various degrees in several neoplastic and inflammatory diseases. In this review, we cover two types of Langerhans cell neoplasms, the Langerhans cell sarcoma (LCS) and Langerhans cell histiocytosis (LCH), represented as either neoplastic or inflammatory diseases caused by MCPyV. METHODS: We meta-analyzed both our previous analyses, composed of quantitative PCR for MCPyV-DNA, proteomics, immunohistochemistry which construct IL-17 endocrine model and interleukin-1 (IL-1) activation loop model, and other groups' data. RESULTS: We have shown that there were subgroups associated with the MCPyV as a causal agent in these two different neoplasms. Comparatively, LCS, distinct from the LCH, is a neoplastic lesion (or sarcoma) without presence of inflammatory granuloma frequently observed in the elderly. LCH is a proliferative disease of Langerhans-like abnormal cells which carry mutations of genes involved in the RAS/MAPK signaling pathway. We found that MCPyV may be involved in the development of LCH. CONCLUSION: We hypothesized that a subgroup of LCS developed according the same mechanism involved in Merkel cell carcinoma pathogenesis. We proposed LCH developed from an inflammatory process that was sustained due to gene mutations. We hypothesized that MCPyV infection triggered an IL-1 activation loop that lies beneath the pathogenesis of LCH and propose a new triple-factor model.

Efficacy and safety of pancreatic juice cytology by using synthetic secretin in the diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect in its early stages with the poorest prognosis of all cancers. To improve the prognosis, a precise diagnosis is needed when we suspect PDAC. Although endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is a widely accepted modality for the diagnosis of PDAC, its sensitivity is 85-89%, and approximately 10% of PDAC cases cannot be diagnosed. The main causes that interrupt the diagnosis of PDAC by using EUS-FNA are tumor size, presence of a vessel or the main pancreatic duct along the puncture route, and difficulty in withdrawing anticoagulant. Pancreatic juice cytology (PJC), the sensitivity of which is 33.3-65.8%, is a method for the diagnosis of PDAC cases in which carrying out of EUS-FNA is difficult. To diagnose PDAC appropriately, we need to improve the diagnostic ability of PJC. METHODS: We examined PJC using synthetic secretin for 138 cases of pancreatic tumor and pancreatic non-cancerous diseases. RESULTS: Sensitivity of PJC improved from 50.9% to 74.0% as a result of synthetic secretin loading, and 13 PDAC cases that had not been able to be diagnosed with EUS-FNA could be diagnosed pathologically by PJC. Although there were 12 patients with mild pancreatitis (8.7%) as a complication, all were relieved with conservative treatment. CONCLUSION: Adding synthetic secretin to PJC is useful for cases in which it is difficult to carry out EUS-FNA for PDAC.

Aberrant expression of AID and AID activators of NF-κB and PAX5 is irrelevant to EBV-associated gastric cancers, but is associated with carcinogenesis in certain EBV-non-associated gastric cancers.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype of gastric cancer characterized by clinicopathological features including lymphoepithelioma-like histology. Aberrant expression of activation-induced cytidine deaminase (AID) as a genomic modulator was demonstrated through pathogen-related nuclear factor κB (NF-κB) signaling in Helicobacter pylori-associated gastric cancer. To elucidate whether or not AID expression is relevant to carcinogenesis in EBVaGC, immunohistochemical expression of AID and AID-regulatory factors between EBVaGC and EBV-non-associated gastric carcinoma (GC) were evaluated, each using 15 cases of GC with lymphoid stroma (GCLS) and other types of GC. Aberrant expression of AID, NF-κB and paired box 5 (PAX5) were significantly decreased in EBVaGC (0/11, 1/11 and 1/11) compared with in EBV-non-associated GC (7/19, 12/19 and 11/19) (P=0.025, 0.005 and 0.01, respectively); however, no significant difference in c-Myb proto-oncogene expression was identified. AID expression was also decreased in EBV-associated GCLS (0/10) compared with in EBV-non-associated GCLS (3/5). Unexpectedly, decreased expression of NF-κB and PAX5 was observed in GCLS (1/15 and 2/15) compared with in GC without LS (12/15 and 10/15) (P<0.001 and P=0.003, respectively). Decreased AID expression observed in EBVaGC is consistent with the reported molecular characterization of hypermethylation and rare somatic gene mutation in EBVaGC. Only PAX5 was identified to be significantly associated with venous invasion (P=0.022). The results of the present study suggest that pathogen-induced AID expression may be irrelevant to carcinogenesis of EBVaGC, whereas it contributes to carcinogenesis in certain types of EBV-non-associated GC.

SMARCA4-deficient thoracic sarcoma: report of a case and insights into how to reach the diagnosis using limited samples and resources.

SMARCA4-deficient thoracic sarcoma is a recently proposed new entity of soft tissue sarcomas with an undifferentiated round cell morphology that is diagnostically challenging. Here we report a case of this tumor where the diagnosis was established using limited samples and resources. A woman in her early 30s developed two intrathoracic masses. Biopsies for these lesions showed sheets of undifferentiated round/rhabdoid cells that retained SMARCB1 expression. Further analysis revealed a reduced SMARCA4 expression and a complete loss of SMARCA2 expression in tumor cells. Subsequent Sanger sequencing identified a nonsense c.1546A>T (p.516Lys>Ter) mutation in SMARCA4 and confirmed the diagnosis. Our case highlighted clinicopathological correlation and rational use of tissue sections for immunohistochemistry may enable to diagnose this tumor even when only limited samples are available. Recognition of this new entity is important for further understanding of the disease and the future development of specific therapies.

Cerebellar Ganglioglioma in Childhood: Histopathologic Implications for Management During Long-term Survival: A Case Report.

We report the case of a 19-year-old female with cerebellar ganglioglioma that was diagnosed at 4 years of age. Despite treatment with partial resection, radiation, and chemotherapy, residual tumor slowly expanded into the brainstem and upper cervical cord, resulting in nocturnal hypopnea, progressive tetraparesis, and feeding difficulty during 8-10 years of age. Initiation of temozolomide and bevacizumab was effective in preventing further expansion of the tumor, and the patient has been treated at home and in school with noninvasive positive pressure ventilation and gastrostomy. Histopathologic examination of the resected tumor tissue revealed phospho-S6-positive tumor cells of either neuronal or astroglial appearance. This suggests that a higher proportion of cells of glial lineage could be linked to the progression of cerebellar ganglioglioma in childhood. Possible treatment options with mammalian target of rapamycin inhibitors are discussed.

Contrast-enhanced sonography with Sonazoid as a new diagnostic tool for splenic hamartoma: a single case report.

Detection of reticuloendothelial system (RES) cells is essential for the differential diagnosis of splenic hamartoma. Among the imaging techniques using contrast agents phagocytosed by RES cells, contrast-enhanced ultrasonography (CEUS) with Sonazoid is less invasive and less costly than (99m)Tc-labeled colloid scintigraphy. We report a case of non-symptomatic splenic hamartoma in a 40-year-old woman detected as an abdominal tumor by screening ultrasonography. The tumor was 4 cm in diameter, round, slightly hypoechoic, and associated with a cystic lesion. The tumor region was stained on enhanced computed tomography with prolonged enhancement, while the cystic lesion was not. The mass appeared as mainly isointense with partial hyperintensity on T1-weighted and as a mixed hypo- and hyperintense region on T2-weighted magnetic resonance images. (99m)Tc-labeled colloid scintigraphy demonstrated uptake in only the tumor region. CEUS with Sonazoid revealed that the tumor was mainly hypervascular with non-enhanced areas in the early vascular phase, but the hypervascular region appeared also as a hyperechoic area (indicating microbubble phagocytosis) in the post-vascular phase. Thus, CEUS with Sonazoid revealed all three cardinal features of splenic hamartoma: hypervascularity, presence of RES cells, and tissue heterogeneity. Splenectomy and histopathology confirmed the presence of a splenic hamartoma with associated hematoma. CEUS with Sonazoid is a promising new diagnostic tool for splenic hamartoma.

Development of a device for detecting target specimens from EUS-guided FNA samples.

BACKGROUND AND STUDY AIMS: Specimens collected by fine needle are microscopic and contain blood; therefore, the presence of a target specimen within a sample is often difficult to confirm. Although rapid on-site evaluation (ROSE) during endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) is beneficial, many health care facilities are unable to apply this technique due to a lack of cytopathologists. The aim of this study was to develop and validate a device that detects the target specimen within pancreatic tumor EUS-FNA samples. PATIENTS AND METHODS: Fifty-eight consecutive patients with solid pancreatic masses were studied for a preliminary case series at a tertiary-care university hospital (Tottori University Hospital, Yonago, Japan). The material collected was checked with a target sample check illuminator (TSCI) and was evaluated by one cytopathologist. RESULTS: The agreement rate between the TSCI and histopathology was 93.7 %. Further testing procedures were not needed in 91.4 % of patients, and the mean number of needle punctures was 1.2 after a single pass using TSCI. No adverse events were encountered with the procedure. CONCLUSIONS: With the introduction of the TSCI in EUS-FNA, it became possible to both collect the minimum necessary target samples by EUS-FNA and to end further procedures, even without performing ROSE.

Clinical Impact of the KL-6 Concentration of Pancreatic Juice for Diagnosing Pancreatic Masses.

BACKGROUND AND AIM: Pancreatic juice cytology (PJC) is considered optimal for differentially diagnosing pancreatic masses, but the accuracy of PJC ranges from 46.7% to 93.0%. The aim of this study was to evaluate the clinical impact of measuring the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses. METHODS: PJC and the KL-6 concentration measurements of pancreatic juice were performed for 70 consecutive patients with pancreatic masses (39 malignancies and 31 benign). RESULTS: The average KL-6 concentration of pancreatic juice was significantly higher for pancreatic ductal adenocarcinomas (PDACs) (167.7 ± 396.1 U/mL) and intraductal papillary mucinous carcinomas (IPMCs) (86.9 ± 21.1 U/mL) than for pancreatic inflammatory lesions (17.5 ± 15.7 U/mL, P = 0.034) and intraductal papillary mucinous neoplasms (14.4 ± 2.0 U/mL, P = 0.026), respectively. When the cut-off level of the KL-6 concentration of pancreatic juice was 16 U/mL, the sensitivity, specificity, and accuracy of the KL-6 concentration of pancreatic juice alone were 79.5%, 64.5%, and 72.9%, respectively. Adding the KL-6 concentration of pancreatic juice to PJC when making a diagnosis caused the values of sensitivity and accuracy of PJC to increase by 15.3% (P = 0.025) and 8.5% (P = 0.048), respectively. CONCLUSIONS: The KL-6 concentration of pancreatic juice may be as useful as PJC for diagnosing PDACs.

Interleukin-1 loop model for pathogenesis of Langerhans cell histiocytosis.

We propose Langerhans cell histiocytosis (LCH) is an inflammatory process that is prolonged by mutations. We hypothesize that Merkel cell polyomavirus (MCPyV) infection triggers an interleukin-1 (IL-1) activation loop that underlies the pathogenesis of LCH. Langerhans cells (LCs) are antigen presenting cells in the skin. When LCs encounter exogenous antigens, they migrate from the epidermis into draining lymphoid tissues to initiate T-cell activity. It has been proposed that LC migration-related factors, including E-cadherin, matrix metalloproteinase, and Notch ligand induce LCH activity. We found that the tyrosine phosphatase SHP-1, which binds IL-1 receptor-associated kinase 1, is expressed at a significantly higher level in LCH affecting multiple organ systems (MS-LCH) than in LCH affecting a single organ system (SS-LCH). IL-1 stimulates T helper 17 cells and their signature cytokine IL-17 had been a matter of controversy. We detected higher levels of IL-17A receptor expression in MS-LCH than in SS-LCH and proposed an IL-17 endocrine model that could settle the controversy. IL-1 is the first cytokine secreted in response to sensitizers and promotes LC migration from sentinel tissues. Myeloid differentiation primary response 88 (MyD88), downstream of the IL-1 receptor, has functions in both RAS signaling and inflammation, leading to human cell transformation. In 2010, an activating mutation in the B-rapidly accelerated fibrosarcoma gene (BRAF) V600E was found in LCH. This BRAF mutation induces phosphorylation of the extracellular signal-regulated kinase (ERK) that may play an important role with MyD88 in LCH pathogenesis. However, phosphorylated ERK (pERK) is rapidly dephosphorylated by dual specificity phosphatase 6 (DUSP6), and limited proliferation is predicted in BRAF mutant cells. MyD88 binds pERK via its D-domain, thereby preventing pERK-DUSP6 interaction and maintaining ERK in an active, phosphorylated state. We detected MCPyV-DNA in the peripheral blood cells of two out of three patients with LCH in high-risk organs but not in those of patients with LCH in non-high-risk organs (0/12; P = .029). MCPyV infection can trigger precursor LCH cells with BRAF mutation to produce IL-1; the IL-1 loop is amplified in all LCH subclasses. Our model indicates both BRAF mutation and IL-1 loop regulation as potential therapeutic targets.

Cytoplasmic Maspin Expression Correlates with Poor Prognosis of Patients with Adenocarcinoma of the Uterine Cervix.

BACKGROUND: Maspin is known to be a tumor suppressor protein and its prognostic significance in patients with several types of cancer has been reported. To date, however, no study has focused on the association between maspin expression and the prognosis of patients with adenocarcinoma of the uterine cervix. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with adenocarcinoma of the uterine cervix. METHODS: Paraffin-embedded tissue samples from 46 patients diagnosed as adenocarcinoma of the uterine cervix were immunohistochemically analyzed using an antibody for maspin. The patients were followed up for 3 to 165 months (median: 64.2 months) and the prognostic value was evaluated by the log-rank test and the Cox regression hazard model. RESULTS: A sample was considered maspin-positive if maspin was expressed in only the cytoplasm; 69.6% (32 cases) of the specimens were maspin-positive, and there was significant correlation between positivity and recurrence (P = 0.022). Maspin-positive patients had both shorter disease free survival and shorter overall survival by the log-rank test (P = 0.023, P = 0.043, respectively). By Cox's multivariate analysis, the International Federation of Obstetrics and Gynecology (FIGO) status was the only independent prognostic factor for disease free survival and overall survival in patients with adenocarcinoma of the uterine cervix. CONCLUSION: This is the first report to reveal an association between cytoplasmic maspin expression and the prognosis of patients with adenocarcinoma of the uterine cervix. Although further studies with a larger series of patients and a longer follow up period are necessary, the present results suggest that cytoplasmic maspin expression could be an indicator of unfavorable prognosis in patients with adenocarcinoma of the uterine cervix.