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.

Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

The purpose of this study was to retrospectively review the pathologic complete response (pCR) rate from patients (n=86) with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012). Stage II patients achieved a higher response rate compared to stage III (P=0.03). The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively) and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively). Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03) and death (HR=0.21; P=0.02). In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

Expression of CD 44 and MIB-1 in serous and mucinous ovarian tumors

In ovarian cancer, alterations in the extracellular environment are critical for tumor Initiation, progression and intra-peritoneal dissemination. Some markers have been used to study the progression of ovarian tumors, one of them is CD44 which shown to play critical roles in ovarian ameer metastasis. Tumor proliferation is known to be important factor in tumor growth. This can be measured by assessment of expression of MIB-1 protein in the tumor cells. To examine the immunohistochemical expression of CD44 and MIB-1 in a spectrum of serous and mucinous ovarian tumors [benign, borderline and malignant tumors] and to evaluate the correlation between intensity of markers expression with relevant clinicopathological criteria [Age, size, hilaterality, gross picture and stage]. Immunohistochemical staining of 120 samples [65 benign, 10 borderline, 30 malignant and 15 metastatic deposits] of spectrum of serous and mucinous ovarian tumors for CD44 and MIB-1 was performed using tissue microarray [TMA] and statistical analyses was done with SPSS [chi-square test]. In whole tumors, expression of [1] 44 in tumor cells [CD-44-T] was low in 20[80%] and high in 5[20%] of benign tumors, low in [70%] and high in 3[30%] of borderline tumors, and low in 24 [83%] and high in 5[17%] of malignant tumors with no significant association in transition from benign to malignant tumours [P 0.70]. Stromal CD44 [CD-44-S] expression was low in 33[94%] and high in 2[6%] of benign mmors, low in 8[80%] and high in 2[20%] of borderline tumors and low in 23[77%] and high in [23%] of malignant tumors with significant association in transition from benign to borderline to 14[CD44-M] showed reactivity in 9[25%] of benign tumors,5[50%] of borderline tumors and 21[72%] of malignant tumors with high significant association in transition from benign to malignant tumors [P<0.001]. In whole tumors, twenty three specimens [31%] showed high PI. All benign tumors had low PI. High significant association was detected between high PI and transition from benign to borderline to malignant tumors [P<0.001] with significant positive correlation between MIB-1 and CD44-M [P 0.013]. Our findings indicates that stromal and membranous expression of with transition from benign to borderline to malignant tumor, so increase in CD44 may play an important role in tumor progression and can be a target of more effective therapies

Proliferative index and p53 expression in breast carcinoma and their correlation to clinico-pathological parameters

Background: Breast cancer is the most frequently diagnosed cancer and the most common cause of cancer deaths in women worldwide. Ki67 is a biomarker that reflects cell proliferation. Despite a clear understanding of the structure and properties of this protein, its functional role remains elusive. Gene expression alteration confers the potential for invasive growth in the preinvasive stages of breast cancer. Altered expression of the tumor suppressor gene p53 is frequently seen in carcinomas of the breast and correlates with poor prognosis. This study aims to investigate Ki67 and p53 expressions in benign, preinvasive and invasive breast lesions and to correlate their expressions with the clinico-pathological parameters

Materials and Methods: This study included 74 specimens of breast lesions. Ki67 and p53 immunostaining expression was detected using avidin-biotin peroxidase method

Results: Ki67 and p53 increased progressively along the continuum of neoplastic changes from normal breast epithelium to invasive ductal carcinomas; IDC [P<0.000 and 1:1<0.01 respectively]. There was significant positive correlation between Ki67-labeling index [LI] and either tumor grade or lymph node metastasis in IDC [11<0.03 and P<0.02 respectively]. P53 expression increased with increasing grade of both ductal carcinoma in situ [DCIS] and IDC [P<0.01 and P<0.002 respectively]. There was significant correlation between p53 and tumor size, lymphovascular invasion, and lymphocytic infiltration [P<0.05, P<0.02. P<0.03 respectively]. There was positive correlation between Ki67 and p53 in both DCIS [r= 0.845, P<0.001] and in IDC [r-0.697, P<0.02] of the breast

Conclusion: Ki67 and p53 increased progressively along the continuum of neoplastic changes from normal breast epithelium to DCIS and IDC. Ki67 and p53 were increased with poor prognostic parameters; tumor size, tumor grade, lymphovascular invasion, lymphocytic infiltration, and lymph node metastasis

Correlation of micro vessel density [MVD] and proliferation index [PI] with clinico-pathological parameters in breast carcinoma

Background: One of the greatest challenges in breast cancer management is to accurately predict the outcome for each patient. Microvessel density [MVD] correlated closely with increasing number of tumor cells shed into the bloodstream and development of metastasis. Because proliferation status closely correlates with tumor aggressiveness, proliferation index [PI] is considered as an established prognostic marker for various tumors. We aimed to: 1. Study WVD and PI by assessing immunohistochemical profiles of CD31 and Ki67 respectively and their probable role in breast cancer progression. 2. Assess values of CD31 and Ki67 in relations to clinico-pathological prognostic parameters

Subjects and methods: Immunostaining was done to detect CD31 and Ki67 expressions in 74 specimens of breast lesions

Results: Both CD31 and Ki67 increased progressively along the continuum of neoplastic changes from normal breast epithelium to invasive ductal carcinomas; IDC [P<0.000 for each]. CD31 expression was positively correlated with minor size [p< 0.04], increasing grade [P<0.01], lymphovascular invasion [p<0.01] and lymph node metastasis [P< 0.05] in IDC. There was significant positive correlation between Ki67 expression and increasing grade [P<0.03] and lymph node metastasis [P<0.02] in IDC. Positive correlation was present between Ki67 and CD31 in ductal carcinoma in situ [DCIS] and in IDC [P<0.02 and P<0.001 respectively]

Conclusion: Our findings indicate that aggressive tumors are more capable of angiogenesis and proliferation which are poor prognostic signs in IDC. These findings might open the door for new therapeutic strategies to prevent progression of DCIS to IDC

NM-23 gene expression and proliferative activity as prognostic indicators in rhabomyosarcoma

To determine nm-23 expression and percentage of Ki-67 labeling index and to correlate these findings with other, rognostic parameters, in rhabdomyosarcoma cases [RMS]. Specimens of 25 cases of rhabdomyosarcoma were studiedfornm-23 antigen immunohistochemically. For evaluation of proliferative activity of tumors, mitotic figures and Ki-67 labeling index were investigated. Ailfindings were analyzed statistically. Fifteen patients were embiyonal rhabdomyosarcoma and ten cases were alveolar rhabdomyosarcoma. Four JMIzents [16%] were stage 1, two [8%] were stage 2, nine [36%] were stage 3 and ten [40%] were stage 4. The percentage of nm-23 positivity was 52%. A significant association was found between nm23 expression and metastasis [p=0.010], where 80% of cases with metastasis at the time of diagnosis showed negative nm-23 expression. On linear regression analysis, Nm-23 expression showed sign[ficant levelfor prediction of metastasis [p=0.042], while initotic figures and Ki-67 labelling index did not reach statistically significant level [p=0.6l9, p=0.062]. These findings suggested that nm-23 expression might be used as a reliable indicator for metastatic potentiality of rhabdomyosarcoma. Further larger prospective studies are neededfor ident ifi cation of other prognostic markers specific for RMS to help us better understand the mechanisms involved in the patho genesis and facilitate the development of novel effective therapies

Determination of the prognostic value of cyclin D1, C-erb B-2, KI-67 and the nucleolar organizer regions [AgNORs] in breast cancer

Four different types of measurements of prognostic factors [cyclin Dl, C-erb B-2, Ki-67 and AgNORs] were applied to a series of 70 breast lesions representing, 35 cases of invasive ductal carcinoma, 10 cases of invasive lobular carcinoma, 5 cases of tubular carcinoma, 10 cases of ducted carcinoma in situ, 10 cases of atypical ductal hyperplasia [ADH], in addition to 7 cases of normal breast tissue as a control, in combination with clinicopathological parameters to evaluate their prognostic significance in breast cancer. Expression of cyclin Dl is negative in atypical ductal hyperplasia [ADH] and ductal carcinoma in situ [DCIS]. However, in 29/50 [58%] of invasive cancer breast, positive expression of cyclin Dl was observed. There is a significant association was observed between cyclin Dl expression and distant metastasis, recurrence, and five-year survival rate of the patients with breast cancer. There is also a significant correlation between C-erb B-2 expression and distant metastases, recurrence and 5-year survival rate. The Ki-67 label index and AgNORs count was found to correlate significantly and increased gradually with progression of breast lesions. The AgNORs size, shape and distribution was found to show a characteristic difference between benign, atypical and malignant groups. Malignant cells were characterized by an irregularly scattered distribution of AgNORs and by a pleomorphic size and shape of the dots in comparison to the round, uniform and regular size and shape of the AgNORs dots in benign lesions. Positive expression of cyclin DI C-erb B-2, Ki-67 and high AgNORs score could be serve as a poor prognostic markers for patients with breast carcinoma independent of nodal metastases and clinical parameters, also expression of cyclin Dl could help in diagnosis of early invasion of breast carcinoma

Investigation of the biological significance of p53 tumor suppressor gene and Ki-67 in colorectal carcinoma resected from Saudi patients: An immunohistochemical analysis

p53 protein accumulation has been shown to be an unfavorable prognostic parameter in many human cancers, but findings in colorectal carcinoma [CRC] are equivocal. The objective of this study is to evaluate the value of p53 and Ki-67 as prognostic markers in patients with colorectal carcinoma. We conducted a retrospective analysis on 56 colorectal cancer specimens resected at King Abdulaziz university hospital, Jeddah, Saudi Arabia [40 cases of left colon and 16 from right colon]. Immunohistochemistry [IHC] was performed on formalin fixed paraffin embedded tissue using the avidin-biotin peroxidase complex method. Antibodies to p53 [DO7] and Ki-67 were used. This was correlated with the following clinicopathologic parameters: patient sex, age and survival; pathological stage, and grade of the tumors. Among the 56 cases of colorectal cancer [male/female=1.3; mean age 54.9 years, range 30-80 years], 85.7% [n=48] of tumors were positive for p13 IHC. Ki-67 was positive in 94% [n=53]. The p53 positivity in different stages was as follows [2/2 stage A, 23/28 stage B, 15/18 stage C and 8/8 stage D]. The positivity of p53 according to tumor differentiation was as follows: [well differentiated 6/6, moderately differentiated 38/45, poorly differentiated 4/5]. P53 was positive in 34/40 of left colon [including rectosigmoid] and in 14/16 of right colon carcinoma. Imunoreactivity for p53 was seen in adenomatous epithelium only in 8/22 cases. Although p53 and Ki-67 expression expresse4 strongly in cancer compared to normal tissue [p<0.05], there was no relation with survival, grade or Dukes' stage of the tumor. P53 cannot be considered as independent prognostic marker in colorectal carcinoma