Atypical Leiomyomas of the Uterus: A Clinicopathologic Study of 54 Cases and an Immunohistochemical Analysis of Ki-67 and p53 / Leiomiomas atípicos del útero: un estudio clínico-patológico de 54 casos y un análisis inmunohistoquímico de Ki-67 y p53

ABSTRACT Objective: Uterine atypical leiomyomas (ALs) are extremely rare and occur in an age group almost one decade earlier than that for leiomyosarcomas. According to the literature, extensive clinicopathologic studies on ALs were limited to only two studies (2, 8). Atypical leiomyomas of the uterus are well-defined neoplasms with smooth muscle cells. The aim of this study was to investigate clinicopathologic findings in 54 cases diagnosed with ALs as well as Ki-67 and p53 expressions immunohistochemically. Methods: Fifty-four cases diagnosed between 2000 and 2013 were included. The histological and clinical features of the cases were reviewed, and their medical records were examined. Ki-67 and p53 were performed on all cases immunohistochemically. Results: The average age of the patients was 41.8 years. The average clinical follow-up period was 57 months. Hysterectomy was performed in 31 patients, and myomectomy in 21 patients, while resection of the mass was performed in two patients due to the intraligamentary mass. The average size of the neoplasms was 6.2 cm. Severe cellular atypia was noticed in 25 patients. While the number of mitoses was 1/10 high power field in 30 patients, it was 4/10 high power field in six patients. Ki67 was found to be positive in 50 patients at the rate of 1-5% immunohistochemically, while p53 demonstrated staining at the ratio of 10-15% staining in four patients. Conclusion: The differentiation of ALs from leiomyosarcomas is crucial. The recurrence rate after follow-up is 2%. In our opinion, the patients diagnosed with 'AL with limited experience' before should be correctly diagnosed as AL. We recommend that Ki-67 and p53 can be used as adjuvant markers immunohistochemically in the patients where a problem in differential diagnosis from leiomyosarcoma exists.

RESUMEN Objetivo: Los leiomiomas atípicos uterinos (LA) son extremadamente raros y se presentan en un grupo de edad casi una década antes que los leiomiosarcomas. De acuerdo con la literatura, los extensos estudios clínico-patológicos en los LA se limitaron a sólo dos estudios (2, 8). Los leiomiomas atípicos del útero son neoplasmas bien definidos con células de músculo liso. El objetivo de este estudio fue investigar los hallazgos clínico-patológicos en 54 casos diagnosticados con LA, así como las expresiones Ki-67 y p53, de forma inmunohistoquímica. Métodos: Se incluyeron cincuenta y cuatro casos diagnosticados entre 2000 y 2013. Se revisaron las características histológicas y clínicas de los casos y se examinaron sus historias clínicas. Ki-67 y p53 se realizaron en todos los casos de forma inmunohistoquímica. Resultados: La edad promedio de los pacientes fue de 41.8 años. El período promedio de seguimiento clínico fue de 57 meses. Se realizaron histerectomías a 31 pacientes, y miomectomías a 21 pacientes, en tanto que a dos pacientes se les realizó resección de la masa debido a la situación intraligamentosa. El tamaño promedio de los neoplasmas fue de 6.2 cm. Se observó atipia celular severa en 25 pacientes. El número de mitosis fue de 1/10 campos de gran aumento en 30 pacientes, en contraste con el número de mitosis de 4/10 campos de gran aumento en seis pacientes. Se encontró que Ki67 fue positivo en 50 pacientes a razón de 1-5% inmunohistoquímicamente, mientras que p53 mostró tinción a razón de 10-15% de tinción en cuatro pacientes. Conclusión: La diferenciación de LA entre los leiomiosarcomas es crucial. La tasa de recurrencia después del seguimiento es de 2%. En nuestra opinión, los pacientes diagnosticados con 'LA con experiencia limitada ' antes, deben ser diagnosticados correctamente como LA. Recomendamos que Ki-67 y p53 sean usados como marcadores adyuvantes inmunohistoquímicamente en los pacientes con un diagnóstico diferencial de leiomiosarcoma.

prognostic value of autotaxin activity and gene expression, matrix metalloproteinase-9 and p 53 antibodies in breast cancer patients

The aim of this study was to analyze changes in autotoxin [ATX] [both enzyme activity and gene expression], metalloproteinase-9 [MMP-9] and p53 antibodies [Abs] serum levels in breast cancer patients and to correlate their results with various clinical, pathological features of breast cancer. Sixty female breast cancer patients [42 with lymph node [LN] metastasis and 18 without LN metastasis] were included in this study and subjected to determination of ATX [both activity by colorimetric method and gene expression by RT-PCR] and both p53 Abs and MMP-9 by ELISA technique. Our results showed that there were statistically significant differences between breast cancer patients with and without LN metastasis in all the studied parameters except for p53 Abs. ATX [both activity and gene expression] and the serum levels of both MMP-9 and p53 Abs, were significantly different between different stages and grades of breast cancer patients with increasing activity and levels from stage I to IV and from grade I to III. Only ATX [both activity and expression] was significantly different between patients with tumor size less than or more than 5. There was a highly significant correlation between ATX activity and gene expression. The present study suggested that ATX activity, MMP-9 and p53Abs could serve as useful and convenient prognostic and detection markers of metastasizing breast cancer. Also, ATX activity may be used as an index for increased ATX gene expression

Detection of B cell lymphoma 2, tumor protein 53, and FAS gene transcripts in blood cells of patients with breast cancer.

Background: Proteins encoded by FAS, BCL-2 and TP53 genes are major regulators of cellular survival and apoptosis. Results of recent investigations show remarkable biological features of these factors, which propose their role in the course of cancer. Therefore, it is plausible to test whether transcripts of these genes could be detected in the peripheral blood cells of patients with breast cancer. Materials and Methods: Real-time polymerase chain reaction assay was performed to detect FAS, BCL-2, and TP53 gene transcripts in the peripheral blood samples of 50 women with histologically confirmed infiltrative ductal carcinoma of the breast. Gene expression of patients was compared with 40 healthy women without history of malignancies or autoimmune disorders. Results: The relative overexpression of BCL-2 in the blood cells from patients of early stages (I and II), nonmetastatic and low-grade tumors compared with healthy individuals, was shown by measuring the gene transcript. Similarly, 3-4-fold higher expression of FAS was found in those patients. The measurement of TP53 transcripts also showed higher levels of gene expression in patients compared with healthy controls. BCL-2 gene expression showed a significant correlation with FAS, while such a correlation was not observed between BCL-2 and TP53 . Conclusion: It seems tumor cells overexpress BCL-2 to inhibit apoptosis and guarantee their cell survival. As a physiologic response, FAS and TP53 could be upregulated to suppress tumors. However, these pathways at early stages of disease may be inadequate and cause progressive malignancy.

[p53 antibodies assay in Syrian mamma carcinoma patients]

The aim of this study was to assay of p53 antibodies in the serum of Syrian breast cancer patients, and to correlate these results with various clinical parameters. We also wanted to assess the prognostic significance of these antibodies in treatment monitoring and recurrence in patients. Serum of 60 patients of breast cancer, 35 patients of benign mass and 35 of control were analyzed using Enzyme linked immunoadsorbent assay ELISA. Eight of sixty breast cancer patients was positive for p53 antibodies [13.3%], one patient of benign mass patients were positive for p53 antibodies [2.9%] and p35 antibodies weren't detected in control group. The difference was statistically significant [p<0.05]. We observed an inverse relationship between the presence of p53 antibodies and the age of the patients. We found no significant association between the presence of p53 antibodies and tumor size. p53 antibodies were higher in patients with metastasis to axillary lymph nodes and advanced stages, but the difference was not statistically significant [p>0.05]. When we followed up patients of positive anti-p53 antibodies after surgery, chemotherapy or radiotherapy, there was a decrease in anti-p53 antibodies as a biomarker as well as a prognostic factor for patients with breast cancer

[Tumor suppressor protein p53 autoantibodies assay in colorectal cancer patients]

Mutation of the p53 tumor suppressor gene is the most common genetic alteration in colorectal cancer, and detection of p53 antibodies in serum might be an effective indirect procedure to detect alterations of the p53 gene. This study aimed to detect the presence of p53 antibodies in patient with colorectal cancer, and to study the association between this antibodies and tumor stage, tumor location, gender, age and smoking. We analyzed serum for p53 antibody using Enzyme linked Immune-adsorbent assay in 57 patients of colorectal cancer and 33 patients of benign disease in gastrointestinal [Crohn's Disease, Ulcerative Colitis] and 35 healthy individuals. Eight of seventy five colorectal cancer patients were positive for p53 antibodies [14%], and p53 antibodies weren't detected in patients with benign gastrointestinal diseases, neither in healthy subjects [control group]. The difference was statistically significant [p<0.05]. We found no significant association between the frequency of anti-p53 antibodies and tumor size, tumor location, gender and smoking. However sero-positive patients were older than sero-negative patients. P53 antibodies are a specific tumor marker of colorectal cancer, and there is no association between the frequency of anti p53 antibodies and tumor size, tumor location, gender and smoking

[ correlation of urine and serum P53 protein in patients with transitional cell carcinoma of urinary bladder]

P53 is a tumor suppressor gene which is mutated in 50% of human cancers. The purpose of this study was to evaluate the association between the protein status in the serum / urine and tumors of bladder cancer. This descriptive study was done on 38 patients with transitional cell carcinoma of bladder who had no history of chemo- or radiotherapy or immune system disease. The sera and urine of these patients were analyzed for P53 protein by Enzyme Linked Immunosorbent Assay [ELISA] and tissue P53 by Immunohistochemical Technique. Individul and laboratory data were collected in questionnaire and analyzed by descriptive statistics and frequency distribution tables. Tissue P53 was detected in 29 of 39 [74.4%] patients, serum and urine P53 protein were detected in the serum and urine of 20 of 39 [51.3%] and 27 of 39 [69.2%] patients, respectively. The mean serum and urine P53 level in positive Tissue P53 patients were 1.45 and 2.27 U/ml respectively, which was significantly higher when compared with mean serum P53 level in negative tissue P53 patients [p< 0.01]. In patients with positive serum P53 [n=20] tissue P53 was positive in 18 [90%] patients and negative in 2 [10%], which was statiscally unsignificant. In negative serum P53 patients [n=19], tissue P53 was negative in 8[42%] patients and positive in 11 [58%]. In patients with positive urine P53 [n=27], tissue P53 was positive in 25 [93%] patients and negative in 2 [%7], which was statiscally unsignificant. Statiscally significant correlation was observed between tissue P53 with pathologic grade of tumor [p= 0.05], but for serum and urine P53 such correlation was not seen. This study shew a strong relationship between tissue P53 protein overexpression and level of P53 protein in serum and urine of TCC patients. Therefore both serum and urine of patients with TCC were found to have significant clinical accuracy for determination of P53 gene status in patients with TCC of bladder

P53 expression and histopathological changes in primary and recurrent pterygia among Egyptian cases

The aim of this work is to assess P53 expression and histopathologic features in the epithelia of both primary and recurrent pterygia cases, searching for the pathogenesis of this common lesion. The pterygia specimens from 22 patients [twelve primary and ten recurrent cases] were studied by both routine hematoxylin and eosin stain and immunohistochemically using antibodies against P53 protein. Cases included in this study were 16 males and 6 females. Their ages ranged from 20 to 55 years. Positive family history was recorded in 18.2% of patients and positive parental consanguinity in 9.1% of them. Twenty cases [90.1%] had a history of chronic exposure to solar light i.e prolonged outdoor exposure time [8-12 hours/day] for more than 5 years. Epithelial hyperplasia was more common in recurrent pterygium samples [8 cases] than primary pterygium [only one case]. But, squamous metaplasia with mild dysplasia was more common in Primary pterygium samples [10 cases] than recurrent samples [2 cases]. Ten out of twelve studied specimens with primary pterygium [83.4%] were positive for abnormal P53 expression and two specimens [16.6%] were negative, while only 2 specimens [20%] of recurrent pterygium showed the abnormal positive expression and 8 cases [80%] were negative. Cases with marked and moderate P53 immunostaining [12 cases] showed squamous metaplasia with mild dysplastic changes, nine out of ten cases with negative immunostaining showed epithelial hyperplasia and the remaining sample showed squamous metaplasia without dysplasia. P53 protein is expressed at a high rate in primary pterygia as compared to cases of recurrence. Hence the possible role of P53 in the original development of pterygium, suggesting that pterygium could be a result of uncontrolled cell proliferation and unregulated cell apoptosis which can be proposed a type of benign tumour or even a precancerous condition and not as a degenerative lesion. It seems to be no correlation between P53 expression and recurrence. Recurrent pterygium was related to hyperplastic changes and this may explain the pathogenesis of recurrence especially if the pterygium was not excised completely and the remained epithelial cells continued to grow and formed a new pterygium

Measurment and evaluation of serum anti p53 antibody levels in patients with lung cancer at its initial presentation

The present study aimed to detect and evaluate anti p53 Ab in patients newly diagnosed lung cancer and its relation to histological type, stage of the disease and response to therapy. For this purpose, 48 lung cancer patients at first presentation. 15 patients proven to have pulmonary disease other than lung cancer and 10 apparently healthy subjects were selected for this study. Ten patients from lung cancer group were followed up after treatment. ELISA procedure was used to detect serum anti p53 antibodies in all subjects. There was statistically insignificant difference between cases with positive and negative anti p53 as regards the mean age and sex. Also percentage of positive anti p53 Ab cases in smokers and those accompanied with pleural effusion were significantly higher than in non smokers and those with no pleural effusion. It was found that 27% of lung cancer patients in this study were anti p53 Ab positive with no cell type difference, as there was no statistical significant difference between different histopathological types as regards the positivity of anti p53 [25% squamous cell carcinoma. 20% adenocarcinoma, 33.3% large cell carcinoma and 25% small cell carcinoma] nor regarding the disease stage. Anti p53 Ab was never detected in association with pulmonary diseases other than carcinoma or in control sera. Ten patients [3 positive for anti p53 and 7 negative] were randomly selected where anti p53 was repeated after 6 months of chemotherapy that led to either partial or complete remission of disease, one of them became negative, the other two positive cases showed reduced titer, in already 7 negative cases before treatment, none of them could find anti p53 Ab after treatment so anti p53 Ab could be a useful tool for oncologists in their attempt to analyze the patient response to therapy