Primary mucinous tumors of the renal pelvis: Clinical, histopathological, and molecular analysis of three cases.

Primary mucinous tumors of the renal pelvis are extremely rare and pose challenges in terms of diagnosis and treatment. This study reviewed the clinical and pathological characteristics of mucinous tumors of the renal pelvis, including mucinous cystadenocarcinomas and mucinous cystadenomas. Immunohistochemical analysis was conducted in three cases, along with KRAS gene detection using the Amplification Refractory Mutation System (ARMS) method. The results revealed mucinous epithelium with acellular mucinous pools in all cases, and acellular mucinous pools were observed in the renal parenchyma and perirenal fat capsules. All tumors expressed CK20 and CDX2, and one case showed KRAS gene mutation. The study suggests that mucinous cystadenomas of the renal pelvis may exhibit borderline biological behaviors. This study is the first to report a KRAS gene mutation in a mucinous cystadenoma of the renal pelvis, offering valuable insights into the diagnosis and treatment of this rare condition.

Mammary mucinous cystadenocarcinoma with long-term follow-up: molecular information and literature review.

BACKGROUND: Mucinous cystadenocarcinoma (MCA) is a very rare form of breast cancer that was first described in 1998. Only 33 cases of primary MCA, including our present case, have been reported thus far. As a consequence, its molecular features, prognosis and treatment regimen are poorly known. Here, we describe a less common presentation of MCA, detail its molecular features, discuss the major differential diagnosis, and provide a brief review of the literature. CASE PRESENTATION: A 59-year-old woman presented with a breast lump in which mammography showed a well-defined nodule. Core needle biopsy (CNB) revealed several lesions lined by tall columnar cells with stratification and abundant mucinous secretion; excision was recommended for final diagnosis. The resected specimens showed cavities of different sizes without surrounding myoepithelial cells. The cavities were rich in mucus, and the nuclei were located at the base of the cells, containing intracellular mucus. Immunohistochemical analysis revealed that it was triple-negative breast cancer (TNBC). Next-generation sequencing (NGS) revealed pathogenic mutations in the PIK3CA, KRAS, MAP2K4, RB1, KDR, PKHD1, TERT, and TP53 genes. A diagnosis of MCA was rendered. The patient has been followed up for 108 months to date and showed no signs of recurrence or metastasis. CONCLUSION: Our study presents the gene profile of an MCA case with no recurrence or metastatic tendency after 108 months of follow-up, and a review of the literature helps us better understand the clinical, pathologic, and molecular features of this tumor.

Genetic profile of primary mucinous cystadenocarcinoma of the breast-A case report.

Primary mucinous cystadenocarcinoma of the breast is a rare neoplasm with few reports in the literature. Here, we report for the first time a comprehensive genetic profile of a primary mucinous cystadenocarcinoma of the breast, using next-generation sequencing 580 cancer-associated gene panel. Mutations in TP53, RB1, and BAP1 were identified. The findings suggest that this tumor is driven mostly by abnormalities in tumor suppressor genes, primarily involved in cell cycle control and chromatin remodeling. Molecular characterization of additional primary mucinous cystadenocarcinomas of the breast is warranted and might provide information related to its biology and behavior.

miR­224­5p regulates the proliferation, migration and invasion of pancreatic mucinous cystadenocarcinoma by targeting PTEN.

Pancreatic mucinous cystadenocarcinoma (MCC) is a rare malignant tumor, with a limited number of studies. The present study aimed to investigate the function and mechanism of microRNA (miR)­224­5p on proliferation, migration and invasion of MCC of the pancreas. Reverse transcription­quantitative PCR was used to explorethe expression of miR­224­5p and the PTEN gene. MTT, wound healing, Transwell and tumorigenesis assays were conducted to investigate the proliferation, migration and invasion of MCC1 cells in vitro and in vivo. Western blot analysis was employed to test the protein expression of PTEN. The target gene of miR­224­5p was assessed and verified by luciferase assay. miR­224­5p expression was notably higher, while PTEN expression was lower, in MCC1 cells compared with normal tissues and cells. Overexpression of miR­224­5p promoted the proliferation, migration and invasion of MCC and knockdown of miR­224­5p inhibited these functions. Bioinformatics analysis and luciferase assay indicated that PTEN was the direct target gene of miR­224­5p. The negative correlation between miR­224­5p and PTEN was confirmed both in vitro and in vivo. PTEN reversed the effects of miR­224­5p on proliferation, migration and invasion of MCC1 cells. The present study revealed for the first time, to the best of the authors' knowledge, that miR­224­5p was highly expressed and served an oncogenic role in MCC. miR­224­5p not only regulated the proliferation, migration and invasion of pancreatic MCC but may also be a potential therapeutic target for MCC.

Primary Mucinous Cystadenocarcinoma of the Breast: A Rare Case Report With Review of Literature.

Primary mucinous cystadenocarcinoma (MCA) of the breast is a rare variant of breast carcinoma known to have a favorable prognosis despite showing a basal-like phenotype. We describe a case of MCA breast in a 45-year-old female with a palpable mass in the breast. On the basis of the histopathological and immunohistochemical evaluation of a lumpectomy specimen with the absence of mass anywhere else on whole-body imaging, a diagnosis of primary MCA was rendered. Mismatch repair protein evaluation showed this tumor to be microsatellite stable. Molecular testing revealed the absence of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. To date only 27 cases of MCA breast have been reported. To the best of our knowledge, ours is the first case documenting diffuse Cytokeratin 20 (CK20) positivity, microsatellite stability, and the absence of KRAS, NRAS, and BRAF mutations in these tumors. The rarity of this tumor further evokes an interest in this case. A better understanding of the disease warrants a review of more cases with longer follow-ups.

Vitamin D regulates cell viability, migration and proliferation by suppressing galectin-3 (Gal-3) gene in ovarian cancer cells.

Vitamin D deficiency is identified as a risk factor for the occurrence and recurrence of ovarian cancer. Galectin-3 (Gal-3) participates in many physiological and pathological processes. In present study, serum vitamin D level was detected using chemiluminescence enzyme immunoassay. Gal-3 expression was examined using real-time polymerase chain reaction (PCR), Western blot and immunocytochemistry analysis. SKOV3 cells viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, the migration of SKOV3 cells was detected using transwell assay, and the proliferation of SKOV3 cells was measured by 3H-thymidine incorporation (3H-TdR). Our study demonstrated that vitamin D levels were lower in 40 ovarian cancer patients: vitamin D deficiency is closely related to the pathogenesis of ovarian cancer. Treatment with vitamin D reduced the migration and proliferation of ovarian cancer cells. Gal-3 was overexpressed in ovarian cancer, which could induce the viability, migration and proliferation ability of ovarian cancer cells, and these effects were abrogated by vitamin D downregulating the expression of Gal-3 gene. Therefore, our results support that vitamin D may suppress Gal-3-induced viability, migration and proliferation ability of ovarian cancer cells, which suggests that the use of vitamin D may have beneficial effects in preventing and treating ovarian cancer.

Ovarian mucinous tumors with mural nodules: immunohistochemical and molecular analysis of 3 cases.

BACKGROUND: Primary ovarian mucinous tumors with mural nodules are very rare. The histogenesis of the mural nodules remains unclear. METHODS: We investigated the clincopathological and molecular features in 3 cases with mural nodules. RESULTS: Patient 1 was diagnosed as mucinous carcinoma with mural nodules of anaplastic carcinoma that was composed of CK+ and CK7+ spindled cells and polygonal cells with marked pleomorphism. Aberrant p53 staining was found in the mural nodules rather than in the mucinous components. A concordant KRAS mutation (c.35G > A p.G12A) was identified in both mucinous tumors and mural nodules. She died of disease at 44 months. The mural nodule in patient 2 was interpreted as a sarcoma, no other specified. The uniform short spindle cells were separated by abundant myxoid matrix. They were CD10 + , CCND1-, SMA-, and negative for break-apart BCOR, PHF1, and JAZF1 FISH assay. The adenocarcinomatous component harbored LOH at D18S51 and FGA loci while the sarcomatous component had LOH at D19S433. She had lung metastasis at 18 months and was alive without evidence of disease for 40 months. Patient 3 harbored multiple mural nodules that were composed of vimentin+, focal CK+, atypical spindle cells. A diagnosis of sarcoma-like mural nodules was rendered. She was alive with no evidence of disease for 13 months. No hotspot mutant AKT1, KRAS, HRAS, and PI3KCA alleles were found in patients 2 and 3. CONCLUSIONS: Mural nodules with anaplastic carcinoma or with true sarcomas may represent the dedifferentiation form of mucinous tumors or collision tumors, respectively. The worrisome histology in sarcoma-like mural nodules necessitates meticulous treatment for these patients.

Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas.

AIMS: Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. METHODS AND RESULTS: To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia. CONCLUSIONS: Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.

Urachal carcinoma: from gross specimen to morphologic, immunohistochemical, and molecular analysis.

Urachal carcinoma (UrC) is an exceedingly rare neoplasm that develops from the urachus, an embryologic remnant of the urogenital sinus and allantois. The most commonly encountered histologic subtype is adenocarcinoma. The aim of this study is to characterize a series of UrC by morphology, immunohistochemistry, and molecular analysis. We retrospectively investigated seven cases of UrCs and assessed patient symptoms, imaging, histologic features, immunohistochemical profile, molecular characteristics, pathologic stages, and type of treatment. Immunostaining for CK7, CK20, Muc-2, CDX2, GATA3, ß-catenin, and CK34ßE12 was carried out on each neoplasm and on seven non-neoplastic urachal remnants as the control group. Additionally, a mutational analysis was performed using the QIAact Actionable Insights Tumor Panel Kit, which analyzes KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, and RAF1. Our cohort comprised five females and two males with a mean age of 64 years. UrCs consisted of two mucinous cystadenocarcinomas and five invasive, non-cystic adenocarcinomas. Carcinoma antigen expression profile was positive for CK20 and negative for CK34ßE12 and GATA3 in all cases. Five of seven cases stained positively for Muc-2 and CDX2. On the contrary, non-neoplastic urachal remnants were immunoreactive for CK34ßE12, CK7, and GATA3. Mutational analysis gave a positive result in four out of seven (57.1%) cases. All four positive tumors showed RAS mutation and one an additional mutation in PIK3CA. Urachal tumors exhibit peculiar morphologic, immunohistochemical, and molecular features. Due to the advanced stage at presentation, individualized treatment should be undertaken.

Pseudomyxoma Peritonei as a First Manifestation of KRAS-Mutated Urachal Mucinous Cystadenocarcinoma of the Bladder: A Case Report.

Only 28 cases of pseudomyxoma peritonei (PMP) arising from urachal neoplasms have been reported. We report one example of this extremely rare disease with KRAS mutational status in its spectrum of pathology. A 45-year-old woman presented with urachal frankly invasive mucinous cystadenocarcinoma confined to the dome of the bladder, which clinically manifested as PMP and was not detected at the first surgery. The primary tumour was revealed 6 months later because of its recurrence as PMP. Microscopic investigation revealed tubular adenoma and cystadenocarcinoma communicating with the bladder lumen and transitioning from the urachal urothelium to the mucinous epithelium. A urachal remnant was identified near the neoplasm. On immunohistochemistry, the tumour proved positive for CK7, CK20, CEA, and CDX2. Staining for ß-catenin revealed expression in both the cytoplasm and cell membrane. Mismatch repair protein expression was normal. Somatic KRAS-mutation (G12V) was revealed in tubular adenoma, cystadenocarcinoma, and mucinous carcinoma peritonei and may play an oncogenic role in the malignant transformation of urachal mucosa and the development of PMP.

Expression of c-myc and mutation of the KRAS gene in patients with ovarian mucinous tumors.

We examined the expression of c-myc and mutations in the KRAS gene in ovarian mucinous tumors to explore the pathogenesis of these tumors and the feasibility of targeted gene therapy. Expression of c-myc protein and mutations in the KRAS gene in 24 cases of ovarian mucinous cystadenoma, 46 cases of ovarian borderline mucinous cystadenoma, and 46 cases of ovarian mucinous cystadenocarcinoma were detected using the immunohistochemistry PV-9000 2-step method and polymerase chain reaction-restriction fragment length polymorphism. The positive expression rates of c-myc in ovarian mucinous cystadenoma, borderline mucinous cystadenoma, and cystadenocarcinoma were 0, 39.1, and 65.2%, respectively (P < 0.01), while the mutation rates in KRAS were 0, 39.1 and 13.0%, respectively. The mutation rate of the borderline group was significantly higher, while rates in the other 2 groups were similar (P > 0.05). c-myc was not correlated with clinical stage, pathological grade, or age of patients with ovarian mucinous cystadenocarcinoma or borderline mucinous cystadenoma (P > 0.05), but was correlated with tumor size (P < 0.05). Mutations in KRAS were not correlated with clinical stage or tumor size in patients with borderline mucinous cystadenoma (P > 0.05), whereas it was correlated with age (P < 0.05). In borderline mucinous cystadenoma, c-myc expression and KRAS mutations were not correlated (P > 0.05). c-myc is involved in the formation of ovarian borderline mucinous cystadenoma and mucinous cystadenocarcinoma, and the KRAS gene may contribute to the formation of borderline mucinous cystadenoma.

Aberrant expression of pim-3 promotes proliferation and migration of ovarian cancer cells.

Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.

PDX-1 mRNA expression in endoscopic ultrasound-guided fine needle cytoaspirate: perspectives in the diagnosis of pancreatic cancer.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration is routinely used in the diagnostic work up of pancreatic cancer but has a low sensitivity. Studies showed that Pancreatic Duodenal Homeobox-1 (PDX-1) is expressed in pancreatic cancer, which is associated with a worse prognosis. We aimed to verify whether the assessment of PDX-1 in endoscopic ultrasound-guided fine needle aspiration samples may be helpful for the diagnosis of pancreatic cancer. METHODS: mRNA of 54 pancreatic cancer and 25 cystic lesions was extracted. PDX-1 expression was assessed by Real-Time PCR. RESULTS: In all but two patients with pancreatic cancer, PDX-1 was expressed and was found positive in 7 patients with pancreatic cancer in which cytology was negative. The positivity was associated with a probability of 0.98 (95% CI 0.90-1.00) of having cancer and the negativity with one of 0.08 (95% CI 0.01-0.27). The probability of cancer rose to 1.00 (95% CI 0.97-1.00) for patients positive to both PDX-1 and cytology and fell to 0.0 (95% CI 0.00-0.15) in patients negative for both. CONCLUSIONS: PDX-1mRNA is detectable in samples of pancreatic cancer. Its quantification may be helpful to improve the diagnosis of pancreatic cancer.

Primary mucinous cystadenocarcinoma of the breast with amplification of the HER2 gene confirmed by FISH - case report and review of the literature.

Fifty five-years-old woman was presented to the general surgery upon the palpation of a mass in her left breast. In the excisional biopsy performed, partially cystic tumor of 2 × 1 cm with solid areas was macroscopically observed. After through microscopic examination, the patient was diagnosed as invasive mucinous cystadenocarcinoma and the tumor was found to be ER- and PR-negative and C-erbB2 (2+). In the fluorescent in situ hybridization, HER2/neu gene amplification was observed. Here, we present the clinical, cytological, morphological and immunohistochemical features of a very rare type of breast carcinoma, mucinous cystadenocarcinoma of the breast, with the review of the relevant literature.

PIK3CA mutations in mucinous cystic neoplasms of the pancreas.

OBJECTIVES: Mucinous cystic neoplasms (MCNs) are rare, potentially curable, mucin-producing neoplasms of the pancreas. We have previously reported PIK3CA (phosphoinositide-3-kinase catalytic subunit, p110α) mutations in intraductal papillary mucinous neoplasms, another mucin-producing neoplasm of the pancreas. In this study, we analyzed the presence of PIK3CA and AKT1/PKB (V-akt murine thymoma viral oncogene homolog 1) hot-spot mutations in MCN specimens. METHODS: Using the genomic DNA sequencing of tumor tissues isolated by laser capture microdissection, we evaluated 15 well-characterized MCNs for the E542K, E545K (exon 9), and H1047R (exon 20) hot-spot mutations in the PIK3CA gene and the E17K mutation in the AKT1 gene. RESULTS: A hot-spot mutation (E545K) of the PIK3CA gene was detected in 1 of the 15 MCNs and further confirmed by a mutant-enriched method. Interestingly, this mutation was found to be present only in the high-grade but not in low-grade dysplastic epithelium obtained from this neoplasm and coexisted with a KRAS mutation. No mutations were identified in the AKT1 gene. CONCLUSIONS: Our data, when combined with previous reports on intraductal papillary mucinous neoplasms, indicate that oncogenic activation of the PI3K pathway involving PIK3CA gene mutations can contribute to the progression of mucin-producing neoplasms but not pancreatic intraepithelial neoplasia. PIK3CA status could be useful for understanding their progression to malignancy.

Analysis of microsatellite instability and loss of heterozygosity in ovarian cancer: a study in the population of Espírito Santo, Brazil.

Ovarian cancer is currently the most lethal gynecological malignancy in women. It is a heterogeneous and cytogenetically complex disease previously associated with genomic instability. Our purpose was to analyze microsatellite markers to determine patterns and levels of instability as well as possible correlations with histopathological parameters. Polymerase chain reaction was used to characterize microsatellite instability (MSI) and loss of heterozygosity (LOH) in 24 ovarian tumors at 12 microsatellite loci. A total of 11 samples displayed MSI or LOH. Only low-level MSI was found. Markers D5S346 and CYP11 showed the highest MSI and LOH frequencies. D17S250 LOH was significantly associated with tumor histological type (P = 0.0003), and estrogen receptor α was also associated with tumor histological type (P = 0.048) when a combined analysis of LOH and MSI was performed. Furthermore, LOH was observed in a greater number of markers compared with those displaying MSI. Thus, our results support that MSI is less common than LOH in ovarian cancers.

Expression of deleted in liver cancer 1 and plasminogen activator inhibitor 1 protein in ovarian carcinoma and their clinical significance.

BACKGROUND: The deleted in liver cancer 1 (DLC1) and plasminogen activator inhibitor 1 (PAI-1) are known to be closely associated with tumor growth and metastasis in several kinds of human tumors. The aim of this study was to investigate the expression of DLC1 and PAI-1 in ovarian carcinoma, and evaluate their relations with the prognosis of ovarian carcinoma. METHODS: Immunohistochemical staining and Western blot were used to examine the expressions of DLC1 and PAI-1 protein in 25 specimens normal ovarian tissues, 52 specimens of serous cystadenocarcinoma tissues and 23 specimens of mucinous cystadenocarcinoma tissues. Chi-square test, Logistic regression and Partial Correlate analysis were performed to evaluate the association between DLC1 and PAI-1 with clinicopathological characteristics. Overall survival was estimated by Kaplan-Meier curves and multivariate Cox analysis. The relationships between DLC1 and PAI-1 protein expression were analyzed by Pearson's correlation coefficient. RESULTS: The expression of DLC1 protein in ovarian carcinoma tissues was significantly lower than that in normal ovarian tissues, but it was converse for PAI-1. In ovarian carcinoma, the expression of DLC1 was significantly associated with advanced FIGO stage, ascites and positive lymph node metastasis, whereas PAI-1 protein was closely related with advanced FIGO stage, poor histological differentiation and lymph node metastasis. The expression of DLC1 was negatively correlated with PAI-1 in ovarian carcinoma. Ovarian cancer patients with negative expression of DLC1 and positive expression of PAI-1 had the worst overall survival time compared to other patients. CONCLUSIONS: The expression of DLC1 and PAI-1 were closely related with the metastasis and invasion of ovarian carcinoma, only the combination of DLC1 and PAI-1 could serve as an independent prognostic factor of ovarian carcinoma.

Molecular pathways in pancreatic carcinogenesis.

Pancreatic cancer is a genetic disease. Pancreatic cancers develop from one of three precursor lesions, pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs), and each arises in association with distinct genetic alterations. These alterations not only provide insight into the fundamental origins of pancreatic cancer but provide ample opportunity for improving early diagnosis and management of cystic precursors.

Molecular abnormalities in ovarian carcinoma: clinical, morphological and therapeutic correlates.

The histopathological classification of ovarian surface epithelial carcinomas (referred to hereafter as 'ovarian carcinoma') has shifted over the past 10 years to reflect more clearly our understanding of molecular events during carcinogenesis. Ovarian carcinoma is no longer viewed as a single entity but as multiple disease processes, with each having different molecular pathways altered during oncogenesis, resulting in differences in clinical and pathological features, such as biomarker expression, pattern of spread and response to chemotherapy. There are five subtypes of ovarian carcinoma that are sufficiently distinct and well-characterized that they should be considered to be different diseases, i.e. high-grade serous, clear cell, endometrioid, mucinous and low-grade serous, from most to least common, respectively. This review summarizes the molecular abnormalities of these five ovarian carcinoma subtypes, relating them to clinical and pathological features.