Immunohistochemical expression of insulin-like growth factor-1Ec in primary endometrial carcinoma: Association with PTEN, p53 and survivin expression.

Chronic hyperinsulinemia due to insulin resistance and elevated levels of insulin-like growth factor (IGF)-1 and IGF-2 are suggestive of a significantly higher risk of endometrial carcinoma. There is a wealth of evidence showing differential expression of IGF-1 isoforms in various types of cancer. In the present study, 99 archived endometrial carcinoma tissue sections were retrospectively assessed by immunohistochemistry for IGF-1Ec isoform expression. Expression of IGF-1Ec was also assessed in nine cases of non-neoplastic endometrial tissue adjacent to the tumor, in 30 cases with normal endometrium and in 30 cases with endometrial hyperplasia. Furthermore, the association between IGF-1Ec and the concurrent expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p53 or survivin was assessed, as well as their combined expression in association with clinicopathological variables. In endometrial carcinoma, IGF-1Ec expression was high in non-endometrioid carcinoma (serous papillary or clear cell carcinoma) compared with that in endometrioid adenocarcinoma. IGF-1Ec expression was also high in the presence of tumoral necrosis. Furthermore, there was a significant correlation between the histological differentiation and the sum of staining intensity and the number of IGF-1Ec immunopositive cells in endometrial carcinoma. There was a moderate negative correlation between co-expression of IGF-1Ec and PTEN, for both the number of immunopositive cells (P=0.006, ρ=-0.343) and the sum of staining (scores and intensity; P=0.006, ρ=-0.343). Furthermore, there was a positive correlation between the sum of staining (scores and intensity) and co-expression of IGF-1Ec and survivin (P=0.043, ρ=0.225). However, there was no association between concomitant expression of IGF-1Ec and p53. These results emphasized the importance of IGF-1Ec expression during development of non-estrogen dependent endometrial adenocarcinoma. IGF-1Ec and PTEN may function opposingly during endometrial carcinogenesis. By contrast, IGF-1Ec and survivin may share common molecular pathways and may promote, in parallel, tumoral development.

Expression of anti-apoptotic protein survivin in human endometrial carcinoma: Clinical and pathological associations as a separate factor and in combination with concomitant PTEN and p53 expression.

Endometrial carcinoma is one of the most common types of gynecological cancer. A total of 99 cases of primary endometrial carcinoma were investigated for survivin expression by immunohistochemistry. Furthermore, the association between concomitant survivin, PTEN and p53 expression, and clinicopathological parameters was examined. Immunopositivity for survivin was identified in 88% of cases. Concomitant survivin, PTEN and p53 expression (staining scores and intensity) was observed in 60% of endometrial adenocarcinomas. A significant association was identified between the sum of staining intensity and scores of survivin immunopositive cells, and patient age (P=0.028), histological grade (P<0.001), clinical stage (P=0.018) and fallopian tube and/or ovarian invasion (P=0.039). A negative tendency for correlation was observed between surivin and PTEN immunostaining scores (P=0.062; ρ=-0.238). Specimens with high scores of survivin expression tended to show decreased scores of PTEN immunostaining, and vice versa. However, in circumstances with an increased co-expression of survivin and PTEN, a statistically significant association with histological types was observed (P=0.020). A statistically significant positive correlation was identified between survivin and p53 sum co-expression (P=0.008; ρ=0.300). Furthermore, a significant association was identified between survivin and p53 concomitant sum expression and age of patients (P=0.001), histological type (P=0.020), clinical stage (P=0.037), histological differentiation (P=0.001) and presence of fallopian tube and/or ovarian invasion (P=0.026). The present findings suggested that survivin may be an indicator of unfavorable outcome in older patients with endometrial carcinoma, in specific circumstances that are dependent on different concomitant genetic alterations and different combinations of molecular signaling pathways. Increased expression levels of survivin and PTEN may serve a role in the development of more aggressive endometrial carcinoma during their interaction. In addition, protein expression levels of survivin and p53 are positively correlated and may share a common molecular pathway to promote endometrial carcinogenesis. These findings provided evidence that survivin and p53 combined may be useful markers for the prediction of tumor behavior and prognosis.

Understanding the Interplay between COX-2 and hTERT in Colorectal Cancer Using a Multi-Omics Analysis.

BACKGROUND: Cyclooxygenase 2 (COX-2) is involved in the initial steps of colorectal cancer (CRC) formation, playing a key role in the catalysis of arachidonic acid to prostaglandin E2 (PGE2). The human telomerase reverse transcriptase (hTERT or TERT) also plays an important role in colorectal cancer growth, conferring sustained cell proliferation and survival. Although hTERT induces COX-2 expression in gastric and cervical cancer, their interaction has not been investigated in the context of CRC. METHODS: COX-2, PGE2 levels, and telomerase activity were evaluated by immunohistochemistry, ELISA, and TRAP assay in 49 colorectal cancer samples. PTGS1, PTGS2, PTGES3, TERT mRNA, and protein levels were investigated using RNA-seq and antibody-based protein profiling data from the TCGA and HPA projects. A multi-omics comparison was performed between PTGS2 and TERT, using RNAseq, DNA methylation, copy number variations (CNVs), single nucleotide polymorphisms (SNPs), and insertions/deletions (Indels) data. RESULTS: COX-2 expression was positive in 40/49 CRCs, bearing cytoplasmic and heterogeneous staining, from moderate to high intensity. COX-2 staining was mainly detected in the stroma of the tumor cells and the adjacent normal tissues. PGE2 expression was lower in CRC compared to the adjacent normal tissue, and inversely correlated to telomerase activity in right colon cancers. COX-1 and COX-2 were anticorrelated with TERT. Isoform structural analysis revealed the most prevalent transcripts driving the differential expression of PTGS1, PTGS2, PTGES3, and TERT in CRC. COX-2 expression was significantly higher among B-Raf proto-oncogene, serine/threonine kinase, mutant (BRAFmut) tumors. Kirsten ras oncogene (KRAS) mutations did not affect COX-2 or TERT expression. The promoter regions of COX-2 and TERT were reversely methylated. CONCLUSIONS: Our data support that COX-2 is involved in the early stages of colorectal cancer development, initially affecting the tumor's stromal microenvironment, and, subsequently, the epithelial cells. They also highlight an inverse correlation between COX-2 expression and telomerase activity in CRC, as well as differentially methylated patterns within the promoter regions of COX-2 and TERT.

Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression.

Endometrial carcinoma is a common malignancy of the female genital tract. Alterations in the expression levels of various oncogenes and tumor suppressor genes serve important roles in the carcinogenesis and biological behavior of endometrial carcinoma. The aim of the present study was to evaluate the combination and individual expression of p53 and phosphatase and tensin homolog (PTEN) protein in human endometrial carcinoma. In addition, the correlation of these proteins with clinicopathological parameters was also assessed. Retrospective immunohistochemical analysis of the expression of p53 and PTEN tumor suppressor proteins was conducted in 99 women with endometrial carcinoma. The overall rate of p53 and PTEN positivity was 89 and 77%, respectively, according to the sum of stain intensity and scores of immunopositive cells. The sum of p53 positivity correlated strongly with PTEN expression (ρ=0.256; P=0.044). The concomitant sum of p53 and PTEN expression was identified in 45% of patients with endometrial adenocarcinoma. Notably, the sum of the immunohistochemical expression of p53 was significantly correlated with patient age (P=0.037), histologic type (P=0.008), histologic grade (P=0.002) and fallopian and/or ovarian invasion (P=0.014). Furthermore, PTEN expression was associated with myometrial invasion (ρ=-0.377; P=0.002) and clinical stage (P=0.019). In addition, concomitant p53 and PTEN expression was correlated with patient age (P=0.008) and histologic differentiation (P=0.028). The findings indicated a correlation between the expression of p53 and PTEN in endometrial adenocarcinoma, which suggested an intrinsic association between expression levels of these tumor suppressor genes. The study also suggested that concomitant p53 and PTEN expression contributed in characterizing the tumor behavior of endometrial carcinoma. Taken together, the present study suggested the combined expression of p53 and PTEN in the development of high-grade endometrial carcinoma in older patients. In addition, the findings indicated activation of different molecular pathways in the tumor progression between low-grade and high-grade endometrial carcinomas.

Histological Comparison of the Human Trunk Skin Creases: The Role of the Elastic Fiber Component.

OBJECTIVE: Skin creases are features of major anatomical, morphological, surgical, and functional interest. This study focuses on the histological comparison of creases of the trunk and participation of the elastic fibers in their formation. The histological structure is a key consideration for the reconstructive planning of the relevant area and its knowledge may contribute in such direction. METHODS: Fresh cadaver specimens were collected from the inframammary (n = 15), infragluteal (n = 16), and inguinal creases (n = 14), the anterior axillary fold (n = 14), and the surrounding skin (n = 10). Specimens were fixed in 10% buffered formaldehyde. Collagen and muscle fibers were stained by Masson Trichrome and Van Gieson stains, reticular and collagen type III fibers by Reticulin stain, and elastic fibers by Verhoef and Orcein stains. RESULTS: Skin creases of the trunk present well-defined dense bundles of collagen fibers, creating a beehive pattern with broad attachment to the dermis and denser in deeper sites related to the fascia of the underlying muscle. The elastic fibers participate in the collagen pattern and radiate in a parallel pattern in the reticular dermis and in a perpendicular fashion in the papillary dermis. The skin surrounding the creases lacks such organization. CONCLUSIONS: Creases of the trunk are formed by well-organized collagen bundles in a beehive pattern, attached to the dermis and related to the underlying muscle fascia. The elastic fibers participate in this structure and radiate in a parallel fashion in the reticular dermis and perpendicularly in the papillary dermis.

Synchronous gastric gastrointestinal stromal tumor and colon adenocarcinoma: a case report.

Gastrointestinal stromal tumors (GISTs) represent the majority of primary mesenchymal tumors of the gastrointestinal tract. They are generally considered to be solitary tumors and therefore the synchronous occurrence with other primary malignancies of gastrointestinal track is considered a rare event. Here we present the case of a 75-year-old man admitted to our hospital with a 10-day history of gastrointestinal bleeding. Colonoscopy revealed an ulcerative mass of 4 cm in diameter in the ascending colon. Gastroscopy revealed a bulge in the gastric body measuring 1 cm in diameter with normal overlying mucosa. Surgical intervention was suggested and ileohemicolectomy with regional lymph node resection along with gastric wedge resection was performed. Pathologic examination of the ascending colon mass showed an invasive moderately differentiated adenocarcinoma stage III B (T3N1M0). Grossly resected wedge of stomach showed a well circumscribed intramural tumor which microscopically was consistent with essentially benign gastrointestinal stromal tumor (according to Miettinen criteria). The patient did not receive additional treatment. Two years later the patient showed no evidence of recurrence or metastasis.

Pseudosarcomatous myofibroblastic proliferation of the urinary bladder: a rare entity.

Pseudosarcomatous myofibroblastic proliferations are very unusual entities of unknown etiology. Despite its benign nature, this entity can easily be misdiagnosed (both clinically and histologically) as a malignant neoplasm. Hereby, we report a case of a 15-year-old woman who presented to our hospital with a broad-based polypoid mass located in the left posterior wall of the urinary bladder. The patient underwent a transurethral resection of the lesion. Morphologic and immunohistochemical findings suggested the diagnosis of pseudosarcomatous myofibroblastic proliferation. The patient is free of recurrence 5 years after surgery.

Renal failure caused by malakoplakia lesions of the urinary bladder.

Μalakoplakia is a rare inflammatory condition of the urogenital tract. The most frequently affected organ is urinary bladder. This condition has features of a granulomatous inflammation, the pathogenesis of which is not well understood. In this study, we presented a case of urinary bladder malakoplakia associated with advanced obstructive uropathy and renal failure.

Chondrosarcoma of the proximal phalanx of the fourth digit: a rare location.

INTRODUCTION: Cartilaginous tumors involving the small bones of the hands and feet are usually benign such as enchondroma, chondromyxoid fibroma and chondroblastoma. The small bones of the hands and feet are rarely involved by primary chondrosarcoma. Proximal phalanges are the most common sites in the hands, but the fourth digit is the least common site. CASE PRESENTATION: We report a case of a 76-year-old Greek female who presented to our hospital with a painful swollen mass measuring 4.5 × 2.6 cm on the fourth digit of the left hand. The radiograph showed a destructive, permeative lytic tumor of the proximal phalanx with extension into soft tissue. The patient underwent curettage, and the microscopic examination of the specimen revealed grade 2 chondrosarcoma. CONCLUSION: Cartilaginous tumors involving the small bones of the hands and feet are usually benign such as enchondroma, chondromyxoid fibroma and chondroblastoma. Primary chondrosarcoma is the third most common malignancy of bone after myeloma and osteosarcoma, but the small bones of the hands and feet are very rarely involved by chondrosarcoma (1% of all chondrosarcoma). However, in these cases differentiation between a benign lesion and chondrosarcoma may be difficult. Occasionally chondrosarcoma of the hands and feet is associated with multiple recurrences or distal metastasis.

An unusual case of unilateral malignant leydig cell tumour of the testis.

Leydig cell tumour is a benign testicular non-germ cell tumour, and malignant transformation is rare. We report a case of a 35-year-old man who came to our hospital with a painless left testicular mass measuring 1.2 × 1 cm. Histological evaluation of the tumour showed features of a malignant Leydig cell tumour but no infiltration beyond the capsule or metastasis. The small size of the tumour was remarkable.

Clinical, ultrasonographic, computed tomography and histopathological manifestations of ovarian steroid cell tumour, not otherwise specified: our experience of a rare case with female virilisation and review of the literature.

INTRODUCTION: Ovarian steroid cell tumours, not otherwise specified (NOS) are rare sex cord-stromal tumours of the ovary. These tumours should be considered a cause of isosexual precocious puberty in children and virilisation in adults. CASE: We report a case of 40-year-old woman with mental handicap who presented with 3 years of amenorrhea and progressive virilisation. Pelvic ultrasonography identified a 6.19 × 6.15 cm well-defined echogenic-multilobular mass arising from the left ovary. Fluid in the cul-de-sac was noted. Colour Doppler examination with endovaginal ultrasonography showed high vascularity of the tumour with low resistance to flow. A computed tomography (CT) scan of the upper and lower abdomen showed a lobular mass with diaphragms in the left adnexal structure and fluid in the cul-de-sac; no adrenal gland enlargement or additional tumour was detected. Laboratory analysis revealed increased levels of serum total testosterone. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histological examination showed a benign steroid cell tumour, NOS without evidence of necrosis, haemorrhage or invasion. The immunohistochemical study showed that the tumour cells were positive for inhibin, CD 99, Melan A and vimentin and negative to CK AE1, CK AE3, progesterone and estrogen receptors. CONCLUSION: Careful medical history, physical examination, laboratory serum values and imaging studies are helpful in making the pre-operative diagnosis. Steroid cell tumours, NOS are usually benign, unilateral and characterised by the composition of two similar-appearing polygonal cell types. They differ from Leydig cell tumours in the lack of crystals of Reinke in their cytoplasm.

Malignant gastrointestinal stromal tumor presenting with hemoperitoneum in puerperium: report of a case with review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that develop in the wall of the gastrointestinal tract and their diagnosis during pregnancy or puerperium is extremely rare. CASE: A 28-year old patient presented with acute abdomen due to hemoperitoneum from a large mass arising of the small intestine with distended vessels on its top and a ruptured superficial vessel bleeding into the peritoneal cavity. The patient was at the tenth postpartum day of her first pregnancy. The preoperative diagnosis was a possible ovarian or uterine mass. After an emergency exploratory laparotomy a segmental bowel resection was performed, removing the tumor with a part of 3-cm of the small intestine. Histology revealed GIST with maximum diameter of 13 cm and mitotic rates more than 5 mitoses per 50 high power fields with some atypical forms, indicating a high risk malignancy. Immunohistochemical staining of the tumor tissue demonstrated strongly positive reactivity to CD 117 (c-kit) and CD34 in almost all the tumor cells. The patient was treated with oral imatinib mesylate (Gleevec) 400 mg daily for one year. Three years after surgery, the patient was alive without evidence of metastases or local recurrence. CONCLUSION: Considering that only few patients with gastrointestinal stromal tumors have been reported in the obstetrical and gynecological literature, the awareness of such an entity by the obstetricians-gynecologists is necessary in order to facilitate coordinated approach with the general surgeons and oncologists for the optimal care of the patients.

Adenosquamous carcinoma of the pancreas: a case report.

Adenosquamous carcinoma of the pancreas is a rare variant of pancreatic exocrine carcinoma. We report a case of 70 year old man who came to our hospital with abdominal pain, anorexia and jaundice. Imaging of the abdomen showed a mass in the region of the head of the pancreas. Histological evaluation of the pancreatic tumor showed an adenosquamous carcinoma which was extensively infiltrative with perineural invasion, involvement of peripancreatic lymph nodes and all the thickness of the duodenum wall. The tumor exhibited a biphasic malignant growth identified as well to moderate differentiated adenocarcinoma and well to poorly differentiated squamous cell carcinoma.

Adenosquamous carcinoma of the pancreas, a rare tumor entity: a case report.

INTRODUCTION: Adenosquamous carcinoma of the pancreas is a rare variant of exocrine pancreatic tumor. This type of tumor is extremely rare as only few similar cases have been described in the literature. CASE PRESENTATION: We present a case of a 72 years old male patient who was admitted to the hospital complaining of epigastric pain and jaundice. Pancreatic carcinoma of the head was diagnosed and a pylorus preserving pancreaticoduodenectomy was performed. CONCLUSION: This type of cancer is a very aggressive tumor followed by a dismisal prognosis. Multimodality therapy seems to be a reasonable approach but more studies are needed, to propose the most effective treatment.