Tumor-stroma ratio as a new prognosticator for pseudomyxoma peritonei: a comprehensive clinicopathological and immunohistochemical study

Background As a rare clinical tumor syndrome with an indolent clinical course and lack of pathognomonic symptoms, pseudomyxoma peritonei (PMP) is usually diagnosed at an advanced stage. In-depth pathological analysis is essential to assess tumor biological behaviors, assist treatment decision, and predict the clinical prognosis of PMP. The tumor-stroma ratio (TSR) is a promising prognostic parameter based on the tumor and stroma. This study explored the relationship between TSR and the pathological characteristics and prognosis of PMP. Methods PMP patients with complete data who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy were enrolled. The TSR of postoperative pathological images was quantitatively analyzed by Image-Pro Plus. Then the relationship between TSR and the clinicopathological characteristics, immunohistochemical characteristics and prognosis of PMP was analyzed. Results Among the 50 PMP patients included, there were 27 males (54.0%) and 23 females (46.0%), with a median age of 55 (range: 31–76) years. 25 (50.0%) patients were diagnosed with low-grade PMP (LG-PMP), and 25 (50.0%) were diagnosed with high-grade PMP (HG-PMP). There were 4 (8.0%) patients with vascular tumor emboli, 3 (6.0%) patients with nerve invasion, and 5 (10.0%) patients with lymph node metastasis. The immunohistochemical results showed that the Ki67 label index was < 25% in 18 cases (36.0%), 25 - 50% in 18 cases (36.0%) and > 50% in 14 cases (28.0%). The range of TSR was 2 - 24% (median: 8%). The cutoff value of TSR was 10% based on the receiver operating characteristic (ROC) curve and X-Tile analysis. There were 31 (62.0%) cases with TSR < 10% and 19 (38.0%) cases with TSR ≥ 10%. The TSR was closely related to histopathological type (P < 0.001) and Ki67 label index (P < 0.001). Univariate analysis showed that preoperative carcinoembryonic antigen (CEA), preoperative carbohydrate antigen 19–9, pathological type, vascular tumor emboli and TSR influenced the prognosis of PMP patients (P < 0.05). Multivariate analysis showed that preoperative CEA, vascular tumor emboli and the TSR were independent prognostic factors. Conclusions The TSR could be a new independent prognosticator for PMP.

Tumor-stroma Ratio as a New Prognosticator for Pseudomyxoma Peritonei: a Comprehensive Clinicopathological and Immunohistochemical Study

Background: As a rare clinical tumor syndrome, pseudomyxoma peritonei (PMP) is usually diagnosed at an advanced stage. In-depth pathological analysis is essential to assessing tumor biological behaviors, assisting treatment decision, and predicting clinical prognosis of PMP. Tumor-stroma ratio (TSR) is a promising prognostic parameter based on tumor and stroma. This study was to explore the relationship between TSR with pathological characteristics and prognosis of PMP.Methods: PMP patients with complete data who underwent last cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy were collected. The TSR of postoperative pathological images was quantitatively analyzed by Image-Pro Plus. Then the relationship between TSR with clinicopathological characteristics, immunohistochemical characteristics and prognosis of PMP was analyzed.Results: Among the 50 PMP patients included, there were 27 males (54.0%) and 23 females (46.0%), with a median age of 55 (31 - 76) years. The patients with histopathological types of disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA) were both 25 (50.0%), 4 cases (8.0%) with vascular tumor emboli, 3 cases (6.0%) with nerve invasion, and 5 cases (10.0%) with lymph node metastasis. Immunohistochemical results showed that Ki67 label index was < 25% in 18 cases (36.0%) and ≥ 25% in 32 cases (64.0%). The range of TSR was 2% - 24% (median: 8%). The cutoff value of TSR was 10% based on receiver operating characteristic (ROC) curve. There were 31 cases with TSR < 10% while 19 cases with TSR ≥ 10%. It showed that TSR was closely related to histopathological types (P < 0.001) and Ki67 label index (P < 0.001). Univariate analysis showed that preoperative carcinoembryonic antigen (CEA), preoperative carbohydrate antigen (CA) 19-9, pathological types, vascular tumor emboli and TSR influenced prognosis of PMP patients (P < 0.05). Multivariate analysis showed preoperative CEA, vascular tumor emboli and TSR were independent prognostic factors.Conclusion: TSR could be a new independent prognosticator for PMP.

Comparative Study of the Minichromosome Maintenance Proteins Complex (MCM 4/5/6) in Ameloblastoma and Unicystic Ameloblastoma

Introduction. Solid/conventional ameloblastoma (AM) and unicystic ameloblastoma (UAM) are the most frequent benign epithelial odontogenic tumors located in the maxillary region, and their treatment usually consists of extensive surgical resection. Therefore, it is relevant to study molecular markers to better understand the biological behavior of these tumors. The aim of this study was to describe and compare the expression of proteins related to cellular proliferation: Ki-67 and MCM4-6 complex. Materials and Methods. An immunohistochemistry technique was performed, with antibodies against Ki-67, MCM4, MCM5, and MCM6, in 10 AM and 10 UAM tumors. The results were quantified using label index and analyzed statistically. Results. AM and UAM had greater expression of MCM6, followed by MCM5, MCM4, and Ki-67 ( P < .05). Immunoexpression of Ki-67 and MCM5 was exclusively nuclear, whereas the expression of MCM4 and MCM6 was nuclear and cytoplasmic. Conclusion. The results suggest that MCM5 is a trustable cell proliferation marker with higher sensitivity compared with Ki-67 and may be useful to predict the biological behavior of AM and UAM. Despite this, further studies are necessary, including a correlation with clinical parameters to confirm these findings.

Immunohistochemical Expression of Survivin and Its Relationship with Cell Apoptosis and Proliferation in Ameloblastomas

Ameloblastoma behavior is related to the potential of tumor cells to inhibit apoptosis and to initiate a proliferative phase. This study was performed to compare the immunoexpression of Survivin with Bcl-2, Bax, and Ki-67 and to associate them with the histopathological type of each variant of ameloblastoma.Material and Methods. Using the World Health Organization (WHO) criteria for ameloblastoma, 110 cases were selected. The cases were classified as solid/multicystic and unicystic ameloblastomas. Cellular counts of cytoplasmic immunoexpression were assessed for cytoplasmic Survivin, Bcl-2, and Bax, while the nuclear immunoexpression of Survivin and Ki-67 was assessed using label index.Results. Cytoplasmic Survivin and Bcl-2 showed higher percentages of immunoexpression in solid multicystic ameloblastomas compared to unicystic ameloblastomas (P<0.05). Bax, Ki-67, and nuclear Survivin were expressed in higher percentages in unicystic ameloblastomas.Conclusions. Cytoplasmic Survivin and Bcl-2 immunoexpression levels were elevated in relation to Bax immunoexpression, suggesting aggressive ameloblastoma behavior, while Ki-67 and nuclear Survivin immunoexpression may be associated with the type of tumor morphology that influences cellular counts or with the greater capacity for cellular proliferation and tumor growth.

Estudo da expressão citofotométrica do marcador tumoral Caspase-3 no adenocarcinoma de cólon

RACIONAL: O adenocarcinoma de cólon é a segunda causa mais comum de morte por câncer em homens e mulheres, sendo responsável por mais de cinco milhões de mortes por ano. No momento do diagnóstico apenas 70% dos tumores são ressecáveis, 75% são curáveis e 25% poderão ter recorrência da doença. A apoptose é uma das responsáveis pelo equilíbrio homeostático entre as células. Durante o desenvolvimento do processo de degeneração maligna celular o desequilíbrio na apoptose é considerado um dos principais marcos neoplásicos. A caspase-3 é uma das mais importantes moléculas na apoptose, sendo sua efetora principal. Sua expressão e prognóstico têm sido relatados em vários estudos e revisões com seu papel valorizado desde o surgimento do pólipo até a sua transformação maligna, com a taxa de apoptose diminuindo progressivamente. OBJETIVOS: Avaliar a expressão citofotométrica computadorizada do marcador Caspase-3 no adenocarcinoma de cólon; avaliá-lo nas fases evolutivas na classificação modificada de Dukes e comparar sua expressão nos tumores do lado direito e esquerdo do cólon. MÉTODOS: Utilizaram-se 19 casos de câncer recuperados de blocos de parafina confirmados por hematoxilina-eosina e submetidos à técnica imunoistoquímica da estreptavidina-biotina com anticorpo policlonal anti-caspase-3. Após este processo as lâminas marcadas foram submetidas à leitura pelo sistema SAMBA com o software IMUNNO 4.00. Foram analisados três índices: marcagem (Label index), heterogeneidade e densidade óptica. Utilizaram-se a marcagem individual, avaliação da expressão do marcador e grupos definidos de tumores com classificação Dukes e pelo lado do tumor. RESULTADOS: A média do índice de marcagem da caspase-3 foi de 85,24 e da densidade óptica de 39,55. Na classificação Dukes de 12 tipos B tiveram índice de marcagem de 86,20 e a densidade óptica de 37,72 e para os 7 tipos C a área de marcagem foi de 85,66 e a densidade óptica foi de 42,71 não sendo possível identificar diferença em relação a classificação de Dukes. Quanto ao lado do tumor os 11 tumores à esquerda tiveram índice de marcagem de 86,65 e densidade óptica de 43,29 e os 8 à direita tíndice de marcagem de 83,29 e densidade óptica de 39,44 não sendo possível observar diferença estatística significante. CONCLUSÕES: A caspase-3 possui alta expressão individual revelando-se marcador de boa utilidade no estudo do adenocarcinoma de cólon e da fase pró-apoptóica da sua tumorigênese pelo seu alto grau de índice de marcagem e densidade óptica. Em relação à classificação Dukes não houve diferença entre os tipos B e C, como também em relação ao lado direito e esquerdo do cólon.

ON THE CELLULAR SITE OF CORTICOTROPHIN PRODUCTION

ABSTRACT Adenine-14C was administered intravenously to rats at various times after adrenalectomy. The hypophyses were studied by means of autoradiography and differential staining and labelled cells were exactly localized and defined as to type. It was shown that shortly after adrenalectomy the majority of labelled cells were small chromophobes. With increasing time after adrenalectomy a gradual shift appeared, first to large chromophobes and finally to amphophils (a particular type of large chromophobe). One and eight days after adrenalectomy, differential cell counts were performed on the hypophyses and the label index was determined for the cell types defined. The label index for small chromophobes was considerably reduced after eight days, whereas the label index for amphophils remained very high in spite of a marked increase in the number of these cells in the counts. No definite change in labelling could be found for acidophil and basophil cells with increasing time after adrenalectomy. The findings indicate that cells in an active state of synthesis are in a cyclic development, i. e. small chromophobe – large chromophobe – amphophil, with increasing time after adrenalectomy. The interpretation is that chromophobe cells are involved in the new synthesis of corticotrophin (ACTH), and that during greatly increased synthesis they increase in size, finally appearing as amphophils.