P16 Expression in Human Breast Carcinoma and its Relationship to Clinicopathological Parameters.

Background: p16 is a cyclin-dependent kinase inhibitor and a cardinal regulator of the cell cycle. The relationship between p16 overexpression and poor prognosis of breast cancer has been reported in some studies. This study aimed to evaluate p16 expression in breast cancer in comparison to normal breast tissue and determine the association between p16 expression and clinicopathological parameters in breast cancer. Materials and Methods: Paraffin blocks of 110 samples were studied. These included 40 invasive breast carcinoma (tumor group) and normal tissue adjacent to the tumor (tumor control), as well as 30 normal mammoplasty specimens (normal control). Samples were from the pathology archive of Alzahra Hospital, Isfahan, Iran, from 2016 to 2020. p16 expression was studied and compared in these three groups using the immunohistochemistry technique. Moreover, the relationship between p16 expression and age, tumor size, carcinoma subtype, tumor grade, and lymph node involvement was investigated in the tumor group. SPSS version 16 was used to analyze data. Results: p16 expression showed a significant difference between the tumor group and the two control groups with a significantly higher expression in the tumor group. There was a significant direct relationship between the intensity of p16 expression and the number of involved lymph nodes (P < 0.001). No significant relationship was detected between p16 expression and other clinicopathological factors. Conclusion: p16 seems to have a rather significant expression in breast cancer in comparison to normal breast parenchyma. However, among clinicopathological parameters, we found only a direct relationship between lymph node involvement and intensity of p16 expression.

Association of Lymphovascular Space Invasion (LVSI) with Histological Tumor Grade and Myometrial Invasion in Endometrial Carcinoma: A Review Study.

Endometrial carcinoma is one of the most frequent gynecological cancers in developed countries. Lymphovascular space invasion (LVSI), histological grade, and myometrial invasion (MMI) are important prognostic factors of endometrial carcinoma. LVSI is considered an independent poor prognostic factor in endometrial carcinoma. Based on the importance of LVSI, this study aimed to discuss the association of LVSI with tumor grade and MMI. A search of PubMed, EMBASE, Web of Science, Scopus, Google Scholar, and Cochrane Library was carried out to collect related studies. Consequently, most studies showed that LVSI is significantly associated with higher histologic grade and deep MMI.

Relationship between matrix metalloproteinase-9 and some clinicopathological prognostic factors of breast carcinoma.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9), an enzyme with major role in remodeling of extracellular matrix, has been the focus of attention in some previous studies in the field of breast cancer. In the current study the relationship between matrix metalloproteinase-9 and some clinicopathological factors of breast carcinoma has also been evaluated. METHODS: Formalin-fixed and paraffin-embedded tissue specimens from three groups including 40 invasive breast carcinoma (tumor group) and their adjacent normal tissue (tumor control), as well as 40 normal mammoplasty specimens (normal control) were studied. The samples were from the pathology archive of Alzahra Hospital, Isfahan, Iran, from 2016 to 2018. The status of intraepithelial MMP-9 were studied and compared in these three groups using immunohistochemistry. RESULTS: The extent of intraepithelial MMP-9 immunostaining in all positive specimens was 100%. The results of intraepithelial MMP-9 staining intensity was as follow: 12.5% strong, 27.5% moderate, 27.5% mild, and 32.5% negative in tumor group; 17.5% strong, 22.5% moderate, 32.5% mild, and 27.5% negative in tumor control group; and 10% strong, 40% moderate, 27.5% mild, and 22.5% negative in normal control group. Intraepithelial MMP-9 immunostaining intensity showed significant difference between tumor and tumor control groups (P<0.001). Intraepithelial MMP-9 immunostaining intensity showed no significant difference between tumor and normal control groups, and between tumor control and normal control groups (P>0.05). No significant relationship was seen between intraepithelial MMP-9 immunostaining intensity and age, tumor size, tumor grade, and lymph node status in tumor group (P>0.05). CONCLUSION: Intraepithelial MMP-9 expression increases in some breast carcinomas. Normal breast tissue adjacent to carcinoma does not show such increase. However, intraepithelial MMP-9 expression in breast carcinoma does not show any significant relationship with age, tumor size, tumor grade, and lymph node status.

Evaluation of human cytomegalovirus antigen expression in invasive breast carcinoma in a population of Iranian patients.

BACKGROUND: The role of human cytomegalovirus (HCMV) in the development of breast carcinoma is questionable. The aim of this study was to evaluate the expression of the immediate early antigen (IE) of HCMV in breast carcinoma and its association with some clinicopathologic factors in a population of Iranian patients. METHODS: Formalin-fixed and paraffin-embedded tissue blocks from the pathology laboratories of the Azahra and Shahid Beheshti hospitals, Isfahan, Iran, from 2013 to 2016, were used in the study. We used immunohistochemistry and real-time PCR to detect the IE-antigen of HCMV in breast carcinoma, normal tissue adjacent to carcinoma, and normal tissue from mammoplasty specimens. RESULTS: A total of 96 samples were evaluated: 70 invasive breast carcinoma of different histologic subtypes and 26 mammoplasty normal breast tissues. All the samples were negative for IE-antigen expression. No relationship was seen between breast cancer and HCMV in this study. CONCLUSIONS: The results of this study failed to show any relationship between HCMV and the development of breast carcinoma.

Extensive Overgrowth of Sex Cord-Like Differentiation in Uterine Mullerian Adenosarcoma: A Rare and Challenging Entity.

Sex cord-like differentiation has been well documented in endometrial stromal tumors. On the basis of the extent of sex cord differentiation, uterine stromal tumors with this kind of differentiation have been classified into 2 subgroups of endometrial stromal tumor with sex cord-like elements and uterine tumors resembling ovarian sex cord tumor. When extensive, this differentiation has been accompanied with indolent clinical behavior and rather good prognosis in most cases. Sex cord differentiation has been rarely observed in uterine mullerian adenosarcoma. Only 3 cases of such occurrence have been reported in the English literature. Herein, we report a case of uterine mullerian adenosarcoma extensively overgrown by uterine tumor resembling ovarian sex cord tumor in a young woman. The presence of an ovarian sex cord tumor component has been confirmed by immunohistochemistry. To the best of our knowledge, this is the second report of such a case in the English literature.

Primary Hyperoxaluria Diagnosed Based on Bone Marrow Biopsy in Pancytopenic Adult with End Stage Renal Disease.

Inborn errors of metabolism cause increase of metabolites in serum and their deposition in various organs including bone marrow. Primary hyperoxaluria (PH) is a rare inborn error in the pathway of glyoxylate metabolism which causes excessive oxalate production. The disease is characterized by widespread deposition of calcium oxalate (oxalosis) in multiple organs. Urinary tract including renal parenchyma is the initial site of deposition followed by extrarenal organs such as bone marrow. This case report introduces a 54-year-old woman with end stage renal disease presenting with debilitating fatigue and pancytopenia. The remarkable point in her past medical history was recurrent episodes of nephrolithiasis, urolithiasis, and urinary tract infection since the age of 5 years and resultant end stage renal disease in adulthood in the absence of appropriate medical evaluation and treatment. She had an unsuccessful renal transplantation with transplant failure. The patient underwent bone marrow biopsy for evaluation of pancytopenia. Microscopic study of bone marrow biopsy led to the diagnosis of primary hyperoxaluria.

Herbs with anti-lipid effects and their interactions with statins as a chemical anti- hyperlipidemia group drugs: A systematic review.

BACKGROUND: The present systematic review aimed to express the clinical anti-lipid effects of different types of herbs, as well as described studied interactions between herbal remedies and prescribed drugs for hyperlipidemic patients which were based on in vitro experiments, animal studies, and empirical clinical experiences. METHODS: For this systematic review, we explored 2183 published papers about herbal drugs interactions from November 1967 to August 2014, fulfilling eligibility criteria by searching in some databases such as Web of Science, Medline, Scopus, Embase, Cinahl, and the Cochrane database. The main keywords used for searching included: herbal medicine, herbs, statin, lipid, and herb-drug interaction. RESULTS: Among published articles about herb-drug interactions, 185 papers met the initial search criteria and among them, 92 papers were potentially retrievable including a description of 17 herbs and medicinal plants. In first step and by reviewing all published manuscripts on beneficial effects of herbs on serum lipids level, 17 herbs were described to be effective on lipid profile as lowering serum triglyceride, total cholesterol, low-density lipoprotein cholesterol as well as increasing serum high-density lipoprotein level. Some herbs such as celery could even affect the hepatic triglyceride concentrations. The herbal reaction toward different types of statins is varied so that grapefruit or pomegranate was interacted with only some types of statins, but not with all statin types. In this context, administration of herbal materials can lead to decreased absorption of statins or decreased the plasma concentration of these drugs. CONCLUSION: Various types of herbs can potentially reduce serum lipid profile with the different pathways; however, the herb-drug interactions may decrease pharmacological therapeutic effects of anti-hyperlipidemic drugs that should be considered when approved herbs are prescribed.

Systematic review on safety and drug interaction of herbal therapy in hyperlipidemia: a guide for internist.

Because of reporting high side effects related to biosynthetic drugs, recent attention has been paid to the use of herbs instead of chemical drugs to balance serum lipids. The present systematic review aimed to evaluate the safety of herbal medicines and also to assess drug interaction in herbal therapy in treating hyperlipidemia. The international research databases including MEDLINE; Google scholar, Web of Science SciVerse Scopus (SCOPUS); EBSCO Academic Search; Cochrane Central Register of Controlled Trials (CENTRAL); and a Chinese database (China Network Knowledge Infrastructure [CNKI]) were searched from their respective inceptions up to September 2014 with the search terms of "hyperlipidemia", "herbal medicine", "medicine traditional", "extract plant", "Traditional Medicine" and "Chinese Herbal Medicine" without narrowing or limiting search elements. A total of 85 randomized clinical trials (RCTs) studies were finally assessed on human subjects. A notable number of herbal drugs that are commonly used as an anti-hyperlipidemia agent may be interacted with a variety of biosynthetic drugs. In this regard, the most common reported herb-drug reactions were related to anticoagulants, antidepressants, anti-epileptic, anti-inflammatory, and/or even antihypertension and anti-lipidemic drugs. Also, a considerable number of anti-lipidemic drugs of plants origin may be accompanied with metabolic disturbances and serious complications within pregnancy and breast feeding. The main fundamental principles for administration of these drugs include physicians' complete awareness of the effects and interactions of these drugs, educating people not taking these drugs arbitrarily, and closely monitoring the verification and distribution of the drugs in the society.

Sentinel lymph node mapping in early stage of endometrial and cervical cancers.

BACKGROUND: The sentinel lymph node (SLN) is defined as the first chain node in the lymphatic basin that receives primary lymphatic flow. If the SLN is negative for metastatic disease, then other nodes are expected to be disease-free. SLN techniques have been extensively applied in the staging and treatment of many tumors, including melanoma, breast and vulvar cancers. This study aims to evaluate our technique in SLN mapping in early stage endometrial and cervical cancers. MATERIALS AND METHODS: We scheduled a cross-sectional pilot study for patients undergoing staging surgery for endometrial and cervical cancer from November 2012 to February 2014 in Beheshti and Sadoughi Hospitals. Our SLN mapping technique included 1 h preoperative or intraoperative injection of 4 ml of 1% methylene blue dye in the tumor site. At the time of surgery, blue lymph nodes were removed and labeled as SLNs. Then systematic lymph node dissection was completed, and all of the nodes were sent for pathologic examination concerning metastatic involvement. All of the sentinel nodes were first stained with hematoxylin and eosin and examined. Those negative in this study were then stained with immunohistochemistry using anti-keratin antibody. Descriptive statistics, sensitivity, negative predictive values (NPV), false negative (FN) and detection rates were calculated. RESULTS: Twenty-three patients including 62% endometrial and 38% cervical cancers enrolled in the study. Median of SLN count in the endometrial and cervical cancers was 3 and 2, respectively. Among endometrial and cervical cancers, detection rate of metastatic disease was 80% and 87.5%, respectively. The FN rate for this technique was 0 and the sensitivity and NPV are 100% for both endometrial and cervical cancers. CONCLUSION: Considering the lower risk of metastases in early stage of both endometrial and cervical cancers, SLN technique allows for confident and accurate staging of cancer.

Association of Epstein-Barr virus with invasive breast carcinoma and its impact on well-known clinicopathologic parameters in Iranian women.

BACKGROUND: The association between Epstein-Barr virus (EBV) and breast carcinoma in Iranian women is uncertain. We examined EBV latent membrane protein-1 (LMP-1) antigen expression in breast carcinoma and its relationship with clinicopathologic parameters among a population of Iranian patients. MATERIALS AND METHODS: This study was performed on formalin fixed and paraffin embedded tissue specimens with a diagnosis of invasive breast carcinoma archived at one university hospital in Isfahan city, Iran. We used immunohistochemistry to detect LMP-1 of EBV in carcinoma and its adjacent normal tissue. The frequency of LMP-1 expression in breast carcinoma and its relationship with age, tumor size, tumor type, tumor grade and lymph node status were then determined. RESULTS: A total of 80 cases were evaluated including 77 (96.3%) ductal, 1 (1.3%) lobular, 1 (1.3%) medullary and 1 (1.3%) mucinous carcinoma. LMP-1 expression was seen in 6 cases (7.5%) of breast carcinoma whereas normal breast tissue adjacent to carcinoma was negative for LMP-1 in all of the cases. A statistically significant association was seen between EBV and invasive breast carcinoma (P = 0.03). No significant relationship was observed between LMP-1 expression on one hand and age, tumor size, tumor type, tumor grade and lymph node status on the other. CONCLUSION: EBV may play an etiological role in some of the cases of breast carcinoma in Iranian women. EBV expression does not seem to have a significant impact on the major clinicopathologic prognostic determinants of breast carcinoma.

Androgen receptor expression and its relationship with clinicopathological parameters in an Iranian population with invasive breast carcinoma.

BACKGROUND: Androgen receptor (AR) status and its association with prognosis in Iranian breast cancer population are uncertain. We examined AR expression and its relationship with clinicopathological parameters among Iranian patients with invasive breast carcinoma. MATERIALS AND METHODS: This study was performed on formalin fixed and paraffin embedded tissue specimens with a diagnosis of invasive breast carcinoma archived at two University Hospitals in Isfahan city, Iran. Antibodies were used for evaluation of AR, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). Other data were gathered from patients' documents. RESULTS: A total of 70 cases were evaluated including 55 (78.6%) ductal, 9 (12.9%) lobular, 2 (2.9%) medullary, and 4 (5.7%) mucinous carcinomas. Overall, 48.6%, 42.9%, 64.3%, and 57.1% of the samples were positive for ER, PR, AR, and HER2, respectively. Thirty three (47.1%) cases were ER(-) PR(-) and 17.1% were triple negative. AR + cases were younger and more frequently positive for ER and showed less frequently tumor size of > 2 cm. Although tumor grade and stage were relatively higher among AR(-) cases compared to AR(+) ones, the difference between the two groups was not statistically significant. CONCLUSIONS: AR expression was found to be frequently present in breast carcinoma in the studied population. Since half of the ER negative and half of the triple negative tumors were found to be AR positive, AR positive cases may benefit from alternative endocrine therapeutic strategies other than the conventional endocrine-targeted medications.

Effect of green tea (Camellia sinensis) extract on healing process of surgical wounds in rat.

Green tea (Camellia sinensis) has anti-oxidant and anti-inflammatory properties and may enhance wound healing process. The present study, therefore, was aimed to examine the effect of green tea ethanolic extract on wound healing process. For this experimental study, 36 healthy male Wistar rats were randomly designated to three groups of A, B, and C which, respectively treated with, Vaseline + 0.6% green tea extract, Vaseline and normal saline for 21 days. Wounds' length and area were measured by caliper every other day and specimens were taken at 3rd, 12th, and 21st day for microscopical examinations. Data were analyzed by SPSS 16 using survival analysis (Breslow test), repeated measured ANOVA, one-way ANOVA and Mann-Whitney. P < 0.05 was considered as statistically significant. The mean healing duration of surgical wounds in groups A and B was 14.66 and 20.66 (P = 0.018), respectively. Decrease in healing duration in the group A was significantly higher within the first two weeks compared with control groups (P = 0.05). Microscopic examinations also indicated a significant difference in wound healing process between groups A and C throughout the whole study duration as well as groups A and B during the 3rd week of the study (P < 0.05). Green tea extract could help wound healing process, probably effective on surgical wounds healing.

Role of cyclin D1 in breast carcinoma.

BACKGROUND: Breast carcinoma is the most frequent cancer among women with considerable invasive and metastatic behavior. CCND1, the oncogene encoding cyclin D1, is amplified in a substantial proportion of human cancers. Although cyclin D1 overexpression has been reported in up to 50% of human breast cancers, its prognostic impact on breast carcinoma is still controversial. MATERIALS AND METHODS: In this cross-sectional investigation, 89 patients with breast invasive ductal carcinoma enrolled in the study. Tumor tissue samples were stained immunohistochemically for cyclin D1. The marker was semiquantitatively scored using the Allred scoring method and its relationship with ER, PR, and HER2-neu status as well as age, tumor grade and stage was then determined. RESULTS: Cyclin D1 was strong (S), intermediate (I), weak (W), and negative (N) in 19.1%, 44.9%, 14.6%, and 21.3% of the cases, respectively. Estrogen receptor (ER), progesterone receptor (PR), and HER2- neu were positive in 60.7%, 58.4%, and 36% of the cases, respectively. There was a statistically significant reverse relationship between tumor grade and cyclin D1 (P = 0.009). The relationship between cyclin D1 and both hormone receptors was also statistically significant (P = 0.0001). There was no statistically significant relationship between cyclin D1 on one hand and age, stage, and HER2-neu on the other (P > 0.05). CONCLUSION: The reverse relationship between cyclin D1 overexpression and tumor grade as well as its positive relationship with ER and PR in invasive ductal carcinoma suggest that cyclin D1 may directly or indirectly result in maturation and differentiation of tumor cells.

Comparison of placental pathology between severe preeclampsia and HELLP syndrome.

OBJECTIVE: This study was performed to evaluate and compare the placental pathology in patients with severe pre-eclampsia (PE) and HELLP syndrome. Moreover, neonatal birth weight was compared between the two groups. MATERIALS AND METHODS: This cross-sectional prospective study was conducted in Alzahra and Beheshti Hospitals (Isfahan, Iran) between 2007 and 2009. Placentas from 32 patients having severe pre-eclampsia without HELLP (referred to as preeclampsia group) and 25 patients having severe preeclampsia with HELLP syndrome (referred to as HELLP group) were evaluated. The studied parameters included placental weight, chorioamnionitis (either acute or chronic), retroplacental hematoma, placental infarction, intervillous thrombosis, and decidual arteriopathy. Birth weight adjusted for gestational age was also compared between the two groups. RESULTS: We found statistically more significant frequency of retroplacental hematoma in the PE group compared to the HELLP group (P value 0.00). Despite the relatively high frequency of accelerated villous maturation and decidual arteriopathy in both groups, the difference between the two groups regarding these two parameters was not statistically significant. Other placental features did not show any significant difference between the two groups either. The frequency of small for gestational age births showed no statistically significant difference between the two groups. CONCLUSION: Retroplacental hematoma was the only placental pathology that showed statistically significant different frequencies between the two groups. Although this may suggest different underlying pathogenetic mechanisms in these two conditions, further studies are needed to confirm this hypothesis.

The expression of prostate-specific antigen in invasive breast carcinoma and its relationship with routine clinicopathologic parameters.

BACKGROUND: Invasive breast carcinoma is one of the most common cancers of women. Parameters such as lymph node status, tumor grade, and the status of hormone receptors are among the main prognostic determinants of this cancer. Immunohistochemical detection of prostate-specific antigen (PSA) is widely used to identify metastatic prostatic adenocarcinoma. However, its immunoreactivity has been found in some non-prostatic tissues. This study was conducted to assess PSA expression in invasive breast carcinoma and its relationship with routine clinicopathologic parameters. MATERIALS AND METHODS: 100 formalin-fixed and paraffin-embedded invasive breast carcinoma tissue specimens from the pathology archive of Alzahra hospital (Isfahan, Iran) were studied for the expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and PSA by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing PSA staining. The relationship between PSA expression and other markers, age, lymph node status, tumor subtype, and tumor grade was then studied. RESULTS: No association was found between PSA expression on one hand and PR, Her2/neu, age, lymph node status, tumor grade, and tumor subtype on the other. PSA score was reversely correlated with ER expression (P = 0.015). CONCLUSION: Despite the reverse relationship between PSA expression and the immunoreactivity of ER, PSA expression was not correlated with other prognostic factors. Therefore, the detection of PSA by immunohistochemistry does not seem to be a significant prognostic parameter in patients with invasive breast carcinoma.

Determining the relationship between "microvessel density" and different grades of astrocytoma based on immunohistochemistry for "factor VIII-related antigen" (von Willebrand factor) expression in tumor microvessels.

BACKGROUND: Astrocytic brain tumors are the most common primary central nervous system tumors, which are classified into four grades. One of the most important pathologic criteria for the diagnosis of higher-grade astrocytomas (especially glioblastoma multiforme) is microvessel proliferation, particularly in the form of glomeruloid complex. Because tumor angiogenesis is a necessary factor for growth and invasiveness of malignancies, microvessel density (MVD) and intensity of angiogenesis may be used to determine the grade of astrocytomas and plan therapy accordingly. We have planned this study to evaluate the relationship between vwf expression in microvessels and different grades of astrocytoma. MATERIALS AND METHODS: Sixty-four formalin-fixed and paraffin-embedded blocks of surgical specimens with diagnosis of astrocytoma (grades I to IV, each of them 16 blocks) were selected in a simple-nonrandom sampling. Thin sections of tissue blocks underwent immunohistochemical staining for vwf. The stained slides were examined using a light microscope at low (100) and high (400) magnifications. MVD was estimated by calculating the mean number of stained microvessels in three areas of highest vascularization in the high-power field (400). The intensity of staining was determined based on a 3 scale model, in which scores 0, 1, 2, and 3 mean no detectable stain, trace staining, moderate amount of diffuse stain, and strong diffuse staining, respectively. RESULTS: Thirty-six (56%) patients were male and 28 (44%) were female. Scores 0 and 1 of microvessel staining intensity were not observed in any grades studied, but severe staining intensity (score 3) was observed in 18.8%, 37.5%, 56.3%, and 87.5% of grades I, II, III, and IV astrocytomas, respectively. "Vwf vessel index" (MVD staining intensity of microvessels) was 23.84, 25.62, 31.62, and 62.43 in grades I, II, III, and IV astrocytomas, respectively. CONCLUSION: We found a significant relationship between staining intensity of vwf in microvessels and different grades of astrocytomas. The intensity of microvessel stain increases in parallel with increasing tumor grade. Regarding "microvessel density" and "vwf vessel index," the difference is predominantly between grade IV and all other grades. However, there is no other statistically meaningful difference between grades I, II and III.