Vitamin D receptor and progesterone receptor protein and gene expression in papillary thyroid carcinomas: associations with histological features.

PURPOSE: Vitamin D receptor (VDR) and progesterone receptor (PR) expression has been described in papillary thyroid carcinoma (PTC) but data regarding association with tumor histological characteristics and localization of the protein expression are scarce. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens from 45 patients with PTC (cases) were retrieved and tumor histological data were recorded. We analyzed gene and protein expression of VDR and PR and gene expression of vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzymes in follicular cancer cells and the adjacent non-neoplastic thyroid tissue (NNTT). RESULTS: VDR mRNA and protein expression was higher in PTC compared with NNTT (p < 0.05). The protein was globally localized in the cytoplasm and cell membranes of the neoplastic cells in all cases, with differences in intensity. Cytoplasmic positivity was stronger in the majority of cases. Membranous positivity was also evident in cases, whereas in NNTT was generally weak and in a low percentage of the cells. Expression of CYP 24A1, but not CYP27B1, was increased in approximately all PTC specimens and was associated with lymph node metastasis and extrathyroidal extension. PR mRNA was increased in 34% and protein expression was present in 57% of cases, and none of NNTT. PR, but not VDR, mRNA expression was significantly associated with the tumor size (r = 0.645, p = 0.007). CONCLUSIONS: We provide evidence for the expression pattern of VDR, PR and CYP24A1 in the progression of PTC. Rapid anti-tumor responses of vitamin D in PTC may be blocked due to inactivation of local vitamin D metabolism.

Anal canal gastrointestinal stromal tumors - report of a rare case and review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are considered as rare gastrointestinal tumors, and their location in the anal track is exceptionally unusual. We describe the case of a 28-year-old man with anal GIST, and a review of the cases that have been reported so far in the literature. CASE REPORT: The patient was referred for treatment of a gradually enlarging perianal mass. Clinical examination and imaging including orthosigmoidoscopy, transanal ultrasound, and magnetic resonance imaging (MRI) revealed a mass sized 7.5 cm in greatest diameter, in relation with the sphincters, which was excised under general anesthesia. His postoperative course was uneventful and he was discharged on the fourth postoperative day. Pathologic examination revealed characteristics of anal GISTs and further treatment with tyrosine kinase inhibitors was planned. CONCLUSION: Anal GISTs usually present with rectal bleeding and pain, and only sixteen cases have been reported in the literature. MRI is the radiologic examination of choice, while optimal treatment is considered surgery in combination with adjuvant therapy. Long-term follow-up is necessary. Hippokratia 2016, 20(4): 313-316.

Neuroendocrine carcinoma in adenoma of the sigmoid.

BACKGROUND: Neuroendocrine cell tumor in adenoma of the sigmoid is a rare neoplasm coexistence and it is considered as a mixed glandular-neuroendocrine neoplasm. DESCRIPTION OF CASE: An 84-year-old woman underwent surgical removal of a tumor located in the sigmoid, diagnosed as adenocarcinoma on a previous biopsy. On gross examination, apart from the ulcerated tumor, a polyp measuring 2 cm was observed, which histologically corresponded to a villotubular adenoma. In two sites of the adenoma, solid nests of smaller cells were observed, having small amount of cytoplasm, round nuclei with finely stippled chromatin. Mitoses were abundant. These cells were located in the lamina propria and muscularis mucosa, without disturbing the polyp architecture, and showed immunophenotypic characteristics of neuroendocrine carcinoma (NEC). The histologic findings set the diagnosis of mixed adenoma and NEC. The patient remains free of recurrence or metastasis by NEC, after two years of follow up. CONCLUSION: The recognition of NEC in an adenoma will help to avoid potential diagnostic pitfalls. Mixed adenoma and NEC is rare, with uncertain biological behavior. This case reinforces the view that NECs without infiltration of submucosa may have a better prognosis.

Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation.

BACKGROUND: Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial. PATIENTS AND METHODS: Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m(2), epirubicin 75 mg/m(2) and paclitaxel (Taxol) 175 mg/m(2) (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m(2) (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients). RESULTS: Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT. CONCLUSION: IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.

EGFR expression and activation are common in HER2 positive and triple-negative breast tumours.

EGFR has been associated with unfavourable prognosis in patients with triple-negative breast carcinomas, although little is known about EGFR activation in these tumours. In a series of breast carcinomas (archived formalin fixed tumours, n=100), we investigated EGFR phosphorylation status at Tyr992 (pEGFR-Y992) and Tyr1068 (pEGFR-Y1068) by immunohistochemistry, along with EGFR protein expression (extracellular domain), gene amplification status (fluorescent in situ hybridization) and conventional clinicopathologic parameters. EGFR protein was present in 21.9%, while phosphorylation at Y1068 and Y992 was observed in 27.8% and 50.5% of tumours, respectively. None of the tumours showed EGFR gene amplification, whereas 21.1% exhibited chromosome 7 polysomy. The above EGFR parameters were usually not simultaneously detected and were not associated with each other. High grade (p=0.003), lymph node positive (p=0.045), estrogen receptor (ER) negative (p<0.001) tumours often expressed EGFR protein. EGFR-Y992 and Y1068 phosphorylation was inversely associated with ER presence (p=0.023 and p=0.029, respectively) but positively with HER2 expression status (p<0.001 and p=0.002, respectively). The global positivity for any EGFR parameter did not significantly differ between triple-negative and HER2 positive tumours. In conclusion, EGFR phosphorylation is commonly encountered in breast carcinomas, although unrelated to EGFR protein presence and gene amplification. EGFR may appear activated even in cases where the extracellular domain of this protein is not observed with immunohistochemistry. These findings may be useful for further studies aiming at the assessment of EGFR parameters on this type of material.

Immunohistochemical investigation of CD34 antigen in male breast carcinoma.

A total of 30 archival cases of male breast carcinoma were studied immunohistochemically for the expression of CD34 antigen. An obvious CD34 staining was found in three cases. By adding the original CD34-positive case, recently published as unique CD34-stained male breast carcinoma, the number of positive cases comes to four. This case was classified as an invasive papillary carcinoma of solid conformation, whereas the three other cases were invasive ductal carcinomas, not otherwise specified. The aim of this study is to establish whether the CD34 positivity, observed in the case of papillary subtype, was a case-specific finding. CD34 expression in the male breast carcinoma, according to our findings, seems to be neither a feature presented exclusively by a singular case nor a specific immunophenotype characterising a special type. The presence or preservation of CD34 antigen in four totally male breast carcinomas may be considered as a novel finding that supports a relationship between these tumours and the progenitor CD34-positive stem cells, committed to the organogenesis of mammary gland. In this context we hypothesise an origin of male breast carcinoma from the stem cells expressing or not the CD34 antigen according to their stage of differentiation.

Detection of fungi in tissue sections by lectin histochemistry.

A battery of 21 fluoresceinated lectins was tested on sections of paraffin-embedded human tissues to determine which lectin could be used in the microscopic diagnosis of fungal diseases. Three lectins, from Canavalia ensiformis (concanavalin), Triticum vulgare (wheat germ A), and Phytolacca americana (pokeweed [PWM]), were found to react with fungal pathogens commonly encountered in nosocomial infections. Best results were obtained with PWM and succinylated wheat germ A, which, due to their weak reactivity with normal tissues, reacted almost selectively with fungi.

Lectin histochemistry of goblet cells in metaplastic epithelium of human gallbladder.

Goblet cells arising in the intestinal metaplasia of chronically inflamed gallbladder were studied by lectin histochemistry and compared with equivalent cells in the small and large intestine. Overall, metaplastic goblet cells reacted more avidly with the majority of lectins and even expressed receptors for lectins that were unreactive with normal intestinal goblet cells. There was, however, considerable variation in lectin binding from one case to another, as well as among the cells of the same specimen. We thus conclude that metaplastic goblet cells in the gallbladder are different from normal intestinal goblet cells, but do not have a uniform lectin binding profile.

Lectin binding sites in the human gallbladder and cystic duct.

A battery of 18 fluorescein isothiocyanate (FITC) labeled lectins was used to histochemically define the features of epithelial cells in the body, neck and the cystic duct of the human gallbladder. Surface epithelium in all three anatomic locations reacted with all lectins, either diffusely or focally, except for lectin type I from Griffonia simplicifolia and type II from Ulex europaeus. No quantitative differences were noted except for the tendency of some lectins to bind more often to the neck and cystic duct epithelium rather than the body and vice versa. In the body the surface epithelium did not differ from cells lining the crypts. On the other hand, glands of the neck and the cystic duct were essentially indistinguishable one from another but differed from the overlying surface epithelium in so far as they reacted with some lectins which were unreactive with surface epithelium and vice versa. Considerable case to case variation in the expression of lectin binding sites in each of three anatomic areas was noted. No consistent differences were noticed between gallbladders removed for cholecystitis--cholelithiasis and those removed for other incidental reasons. We conclude that all epithelial cells in the cholecysto-biliary tract are rich on glyconjugates but the pattern of expression varies depending on the anatomical location and the influence of poorly understood individual determinants.