Tehran University Medical Journal

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Dispersed neuroendocrine system (D.N.S) consists of a wide variety of cells that are present in the central and peripheral nervous system and in many classic endocrine organs and different tissues such as respiratory and gastrointestinal tracts, skin, prostate, breast and also their neoplasm show neuroendocrine differentiation by electron microscopy, immunohistochemistry or biochemical techniques:
Materials and Methods: The present study has been carried out by case-series method in order to evaluating the characteristics of all types of neuroendocrine carcinoma: different anatomical locations during 5 years period in immunohistochemistry department of cancer institute.
Results: The diagnosis of 109 cases of neuroendocrine carcinoma consisting of neuroendocrine carcinoma, small cell carcinoma, medullary carcinoma of thyroid, carcinoid tumor and merkel cell carcinoma are confirmed that among them the most common diagnosis was related to neuroendocrine carcinoma (50.5 percent). The most prevalent age group was 40-49 years and male to female distribution were 56 percent and 44 percent respectively. Anatomical distribution of tumor show that about 30 percent of cases were metastatic carcinoma, 30 percent in thyroid, respiratory tract and head and neck region and remainder in a variety of tissues. In over 50 percent of cases one of endocrinoid patterns as trabecular, organoid or mixed of them were seen.
Conclusion: Immunohistochemically N.S.E (Neuron Specific Enolase) show high sensitivity with 96 percent positive reaction and more specific endocrine markers as chromogranin A in 80 percent and synaptophysin only in 24 percent because of lesser application of the latter. Also epithelial markers such as cytokeratin and E.M.A.
(Epithelial Membrane Antigen) were positive in 69 percent and 74 percent respectively. Mean survival rate of all neuroendocrine carcinoma reached to 4.8 years with lowest survival of 4.3 years among small cell carcinoma and highest in merkel cell carcinoma with 5.5 years.

 

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Background: Immune deficiency is one of the major causes of morbidity and mortality in the modern world. Primary immunodeficiency comprises a wide range of disorders that mainly manifest in early childhood as devastating infections with opportunistic organisms. Thymic aplasia is found on autopsy of some patients afflicted with immune deficiency disorders, such as DiGeorge syndrome and severe combined immunodeficiency (SCID). After a thorough search of the literature, we found little information on the cellular characteristics of these thymuses. Our study aims to elucidate role of apoptosis in the pathogenesis of thymic aplasia and compare various lymphocytic and epithelial markers in normal and aplastic thymuses.

Methods: We selected 12 subjects who died of severe infections with aplastic thymus found on autopsy, and 11 control subjects who died of unrelated causes, such as congenital heart disease. The presence of several markers, including Bcl2, P53, lymphocytic markers, and CD68, was examined using immunohistochemical methods on paraffin-embedded thymus sections. Positively-stained cells were counted per 1000 cells and the results stated as percentage of positive cells.                       

Results: The mean age of the control group was between 7 days to 18 months (mean: 4.5 months). Parental consanguinity was present in 45.5% and 9.1% of the control and case groups, respectively however, this was not statistically significant. We found significantly lower expression of Bcl2 in the case group (p value: 0.038). Furthermore, expression of CD68 was significantly higher in the case group. Epithelial markers were significantly higher in case subjects, although CD8 expression was higher in the control group. The presence of other markers was not significantly different between the two groups.

Conclusions: Increase in apoptosis has a role in aplastic thymuses and prevention of apoptosis may halt this process. Also high CD68 expression denotes increased phagocytic activity in aplastic thymuses.

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Background: The postmortem diagnosis of early myocardial infarction is a perplexing affair in forensic pathology. The routine evaluations of autopsied hearts including macroscopic examination and study of H&E stained sections are often not contributory. Some other methods like electron microscopy need sophisticated equipments which are not available in all pathology laboratories.

Methods: In an attempt to find a more reliable and less labor- intensive method, we have studied the diagnostic value of cardiac troponin- T by an optimized immunohistochemical method on 67 autopsied hearts in Legal Medicine Organization of Iran. The cases were divided into three groups: the positive group composed of cases with the definite diagnosis of myocardial infarction (MI) as the cause of death the non-cardiac death group and finally the suspicious group which consisted of cases with high probability of early myocardial infarction, however without definite evidence of MI on the routine histopathologic studies. In stained sections, the degree of troponin T depletion was scored.

Results: With our proposed cut off, this test showed positive results in 19 out of 22 cases in MI group (86.4%), none of the 17 cases of non-cardiac death (100% specificity), and 15 out of 28 cases of suspicious group (53.6%).

Conclusions: This relatively easy method may increase the sensitivity of routine histopathologic methods in postmortem detection of early myocardial infarction. Additionally, this method does not require a particular preparation and can be done very easily on the archival paraffin blocks available in pathology departments whenever further evaluation is deemed necessary by the pathologist.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Diffuse large B Cell lymphoma (DLBCL) is the most common subtype of non-Hogkin lymphoma (NHL). We performed a retrospective study of patients with de novo DLBCL treated in the Medical Oncology department of Cancer Institute of Iran, Tehran to assess the clinicopathologic and immunohistochemistry correlation and prognosis of the patients.
Methods: World Health Organization (WHO) classification was used to reexamine 1470 biopsy specimens related to the years 1985-2006. After excluding five cases of T Cell large cell lymphoma, 50 Patients diagnosed as DLBCL.
Results: Median age of the patients was 45.5(20-85) years: 60% were male and 30% had primary extranodal disease. The most common extranodal sites were bone, gastrointestinal tract and Head and neck areas. The most common stages were stage II (32%), stage III (32%), stage IV (20%) and stage I (16%) retrospectively and 33% had B-symptoms. All of The Patients received chemotherapy (83% CHOP regimen) and 46% treated by radiotherapy after chemotherapy. With a mean follow up time of 32 months, median survival time was 34 (95% CI 24-40) months. Prognostic factors for survival were tumor stage, B-symptoms and early relapse (less than 6 months).
Conclusions: Our data showed the importance of Immunohistochemistry method in diagnosis of DLBCL. Although DLBCL is potentially curable with CHOP chemotherapy protocol, addition of monoclonal antibody (Anti CD20) and finding new prognostic factors to predict early relapse are clearly needed in Iran.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Uterine smooth muscle tumors classified as leiomyoma, leiomyosarcoma and tumors with uncertain malignant potential. The leiomyoma and leiomyosarcoma are separated tumors biologically. Uterine smooth muscle tumors with uncertain malignant potential include a group of tumors which are not specifically placed into two others groups which result in a serious problem in a way of their treatment. In the present study expression of marker "p16" in smooth muscle tumors of uterine and normal myometrium has been investigated.
Methods: The entire paraffin blocks related to hysterectomy cases with diagnosis of normal myometrium, leiomyoma and leiomyosarcoma (3768 cases) available in pathology lab. in Shariati Hospital in Tehran, Iran from 1372 to 1387 were investigated. Among them 62 normal myometrium, 62 leiomyoma and 12 leiomyosarcoma had been chosen and after staining for marker "p16" were investigated separately.
Results: There were a statistically significant difference in both intensity and percentage of staining for this marker between leiomyoma and leiomiosarcoma (p< 0.001) and between leiomyosarcoma and normal myometrium (p< 0.001) but not between leiomyoma and normal myometrium (p= 3.6).
Conclusion: Based on this study if strong and more than focal immunoreactivity for marker "p16" suppose as positive then leiomyosarcoma will be positive for this marker but leiomyoma and normal myometrium will not be and this could be considered as a good guide for categorizing the uterine smooth muscle tumors.

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Background: Ewing sarcoma family tumors (ESFTs) are among the most malignant tumors in children and young adults. ESFTs include Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumors (pPNETs). As there seemed to be few studies on the molecular biology of ESFTs, we investigated the frequency of CD99, Ki67, p53 and Fli- 1 protein expression in 15 Iranian patients with ESFTs. In addition, the correlation between expression rate of these proteins and various clinical factors, including age, sex and survival was computed. Methods: The expression of the aforesaid proteins was studied by immunohisto- chemistry in formalin-fixed and paraffin-embedded blocks of 15 ESFTs specimens. Stained sections were classified according to the percentage of stained tumor cells. Results: The results showed the membrane expression of CD99 protein in all of the specimens. The nuclear expression of Fli-1 protein was observed in 86.7% and the over- expression of p53 nuclear protein was seen in 53.3% of the specimens. The expression rate of Ki67 protein was 60%. Although a significant correlation was not shown between the expression levels of Ki67, p53 or Fli-1 proteins with age, sex or survival of the patients, there was a significant correlation between expression levels of p53 and Ki67 proteins (P=0.003). Conclusion: The results underline the role of p53 and Ki67 proteins in the development and progression of ESFTs and suggest the simultaneous immunohistochemical staining of Fli-1 and CD99 proteins for the diagnosis of ESFTs.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Cyclooxygenase 2 is a key enzyme which converts arachidonic acid into prostaglandins. Cyclooxygenase 2 is triggered by inflammatory stimuli, such as cytokines. Its expression increases in tumors and Alzheimer's disease and ovarian hyperstimulation syndrome. Polycystic ovarian syndrome is a heterogeneous disease characterized by pathological angiogenesis and chronic anovulation. In the present study, the probable role of cyclooxygenase 2 in Wistar rats with polycystic ovarian syndrome was investigated.
Methods:  Thirty female Wistar rats (170-200 gr) were equally divided into three groups: 2 mg estradiol valerate was intramuscularly administered to each rat in the experiment group or group 1 the rats in group 2 were regarded as the sham group and received sesame oil injections and group 3 or the control group received no injections. After 60 days of treatment, animals were anaesthetized with chloroform and killed by decapitation. Ovaries were collected for histological and immunohistochemical evaluations. All the experiments were repeated three times.
Results:  Morphologically, ovaries from the control group exhibited follicles in various stages of development and many fresh corpus luteum. In estradiol valerate group small follicles in early development were observed in addition to follicles showing evidence of atresia and many large cysts with thickened theca cell layer. Corpus luteum was rare or absent in group 2. The immunohistochemical analysis for cyclooxygenase 2 expression showed an increased expression of cyclooxygenase 2 enzyme in group 1.
Conclusion: The results suggested the involvement of cyclooxygenase 2 in the progression to polycystic ovarian syndrome in a rat model.

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Background: Endometrial carcinoma (EC) is the most common gynecologic malignancy however, mechanisms underlying its pathogenesis remain obscure. Endometrial carcinoma has been classified into two major categories: type I (related to estrogen or endometrioid adenocarcinoma) and type II (unrelated to estrogen). Estrogen is the main trigger for the abnormal proliferation in the endometrial epithelium but progesterone can inhibit this process. The aim of this study was to analyze the expression of estrogen and progesterone receptors in all types of endometrial hyperplasia in comparison to endometrioid adenocarcinoma of endometrium.

Methods: Forty-seven specimens including 23 cases of histopathologically confirmed hyperplastic endometrium (12 simple hyperplasia, 5 complex hyperplasia without atypia, and 6 complex hyperplasia with atypia) and 24 cases of endometrial carcinoma were studied. Immunohistochemical staining of estrogen and progesterone receptors was performed in paraffin-embedded blocks and expression of estrogen and progesterone receptors were scored according to the proportion of positive staining cells.

Results: Overexpression of progesterone receptors was seen in 18 (75%) out of 24 cases of endometrial carcinoma and 23 (100%) of all types of endometrial hyperplasia. The aforesaid differences were statistically significant (P=0.023). 70.8% of cases with endometrial carcinoma were 3+ for immunohistochemical staining of progesterone receptors as were 85.7% of the cases with endometrial hyperplasia the difference being also statistically significant (P=0.02).

Conclusion: Considering the increased proportion of progesterone receptor expression in all types of hyperplastic endometrium in comparison to endometrial carcinoma, hormonal therapy by progestinal agents is recommended as a treatment of choice.

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Background: Transitional Cell Carcinoma (TCC) is the most common type of urinary bladder cancer. Cyclooxygenase-2 (COX-2), a key enzyme in prostaglandins biosynthesis, has been introduced as a new candidate for targeted therapy in this cancer. In this study, we investigated the expression of COX-2 in urinary bladder TCCs and its relationship with clinicopathological parameters such as tumor grade and stage.

Methods: This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Pathology reports of patients with definite diagnosis of urinary bladder TCCs who had undergone Transurethral Resection (TUR) were reviewed and 40 cases were selected. Subsequently, COX-2 expression was assessed immunohistochemically by the examination of paraffin embedded tissue blocks. Staining in more than 5% of tumor cells was considered as positive expression.

Results: COX-2 was expressed in 52.5% of the patients. High-grade tumors revealed a higher (87.5%) COX-2 expression versus other grades of the lesions and there was a statistically significant difference in COX-2 expression between them (P<0.001). Patients' age was also related to the expression of this marker (P=0.03). In contrast, this marker did not correlate with other characteristics including gender, lymphatic invasion or tumor stage. In addition, perineurial or vascular invasions were not detected in any of the patients.

Conclusion: COX-2 expression was seen in more than half of our patients and it had a marked relation to tumor differentiation. Accordingly, this molecule may be a useful tumor marker in the assessment of urinary bladder cancers.

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Background: Recently the use of “two tier" grading system in which ovarian serous carcinoma was classified as low-grade or high-grade in comparing to preceding system has improved authority in prognosis and survival. This approach is simplistic, reproducible, and based on biologic evidence. In this study, we reclassified ovarian serous carcinoma by a new two-tier system for grading and then evaluation of P53 expression in these tumors by immunohistochemistry method. Methods: We retrospectively reviewed 32 cases of ovarian serous carcinoma with previous diagnosis of well differentiated (eight cases) and moderate to poorly differentiated serous carcinoma (24 cases) and according "two tier" grading system in low-grade vs. high-grade serous carcinoma reclassified. Subsequntly all cases immunostained by P53 marker. Also clinical data related to survival of patients (with or without recurrence of tumor and death) and paraclinical findings such as presurgical blood serum level of CA125 are gathered. Results: Out of total eight patients with previously diagnosis well diferentiated serous carcinoma and of 24 patients with moderate to poorly differentiated serous carcinoma reclassified as low-grade and high-grade ovarian serous carcinoma respectively and a statistically significant difference was found between two groups. (P<0.005) Also of total 24 cases with high grade serous carcinoma, in 12 cases (54%) P53 immunostaining was detected but in non of all low grade serous carcinoma was seen. All 8 low grade serous carcinoma were alive without recurrence of tumor. In 10 and 12 out of 24 cases with high grade serous carcinoma recurrence of tumor and death were seen respectively. Conclusion: Since the presence of P53 negative expression in all of low-grade serous carcinoma by immunostaining and low-grade serous carcinoma accounts for small pupulation of all ovarian serous carcinoma and also few cases in our study, we did not find significant differences between P53 expression and survival in two low-grade vs high-grade serous carcinoma groups.

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Background: The incidence rate of gastric cancer in Western countries has shown a remarkable decline in recent years although it is still the almost common cancer between men in Iran. The proto-oncogene MYC, located at 8q24.1, regulates almost 15% of human genes and is activated in 20% of all tumors. MYC amplification and overexpression of its protein product are observed in 15-30% of gastric neoplasia. The objective of this study was to find the preference of CISH or IHC in the diagnosis and prognosis of gastric cancer. Methods: In this cross-sectional investigation, 102 paraffin blocks samples of Iranian patients with gastric cancers were studied. All the patients had undergone primary surgical resection at the Cancer Institute Hospital, Tehran University of Medical Sciences from 1987 to 1993. CISH and IHC techniques were applied to the samples. CISH was carried out on 3-µm-thick tissue sections and with a ZytoDot CISH Implementation Kit (ZytoVision GmbH, Germany). IHC was down using the HRP method with the monoclonal antibody. A universal peroxidase-conjugated secondary antibody kit was used for the detection system. All samples were gastric adenocarcinoma and were selected randomly. Results: Our data revealed that both diffuse and intestinal types of gastric cancer occurred significantly in men more than women. Our results showed an indication of some correlation between grades and CISH results, although the difference was not significant. Our data also showed that CISH+ patients (43.1%) were more frequent in comparison with IHC+ patients (14.7%). There was a correlation between CISH and IHC. This result revealed that there was a significant difference between grades and IHC. There was also no statistically significant difference between CISH amplification in diffuse and intestinal types. Conclusion: Our conclusion is that for the treatment, management of stomach cancer, and monitoring of progress and prognosis of the tumor that is almost important for patients and clinicians, CISH test is a better and feasible to IHC test, with regards to sensitivity and specificity.

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Background: Breast cancer is the most common cancer in women around the world. It has been known for over a century that androgens and androgen receptor (AR) play a role in normal and neoplastic breast cells. The aim of this study was to determined the AR expression on tumor cells and its correlation with other prognostic and predictive factors as well as contribution of AR in patients overall survival (OS) and disease- free survival (DFS). Methods: This retrospective cross-sectional study performed on 189 patients who referred to Medical Oncology Ward of Cancer Institute, Tehran University of Medical Sciences, from April 2007 to February 2010. We performed an immunohistochemistry study for AR (AR441 clone, Dako, Germany) (10% cut-off point) and Ki-67 MIB-1 clone, Dako, Germany) on paraffin embedded blocks. Other data were extracted from patients’ documents. Results: Overall, AR expression was 49.1%. Mean age of the patients with and without AR was 47.86 and 48.49 years, respectively. AR positive tumors presented more in stage I/II than III/IV (P=0.02) and AR were more positive for estrogen receptor positive, lower grade of tumor (grade I/II versus III) and lower Ki-67 (P=0.01). AR positivity had neither correlation with progesterone receptor, HER2/neu, P53 expression or menopausal status. OS and DFS were higher in AR positive patients but did not reach statistical significance. In triple-negative breast cancer (TNBC) group, 25% of tumors showed AR expression. AR had non-significant positive correlation with OS in TNBC cancer patients. OS and DFS had significant statistic positive correlation with ER, PR and stage regardless of AR status. Conclusion: Based on this study, although androgen receptor expression showed correlation with other prognostic factors for survival in patients, we didn’t find statistically significant independent relationship between AR and overall survival in patients. As far as there isn’t any targeted therapy for triple-negative breast cancer (TNBC), prospective basic and clinical studies regarding AR inhibitors in the treatment of TNBC seems to be logical and valuable.