Clinical significances of TTF-1, neuroendocrine (chromogranin, synaptophysin, CD56), and keratin (pancytokeratin, CK7, CK5/6) marker immunostaining in small cell lung cancer.

PURPOSE: Immunohistochemistry (IHC) markers have established a role in the pathological diagnosis of small cell lung cancer (SCLC) and especially neuroendocrine markers help to differentiate SCLC from other tumors. The study aimed to evaluate the clinical role of different IHC markers in SCLC patients. METHODS: A total of 378 SCLC patients were enrolled in the study and analyzed retrospectively. TTF-1, neuroendocrine markers (chromogranin, synaptophysin, and CD56), and keratin markers (pancytokeratin, CK7 and CK5/6) were assessed. RESULTS: CD56 had the highest expression (92.3%) followed by pancytokeratin (82.8%), TTF-1 (74.8%), synaptophysin (72.7%), chromogranin (55.6%), CK7 (54.8%), and CK5/6 (9%). No differences were observed in the expression of all markers according to the stage of the disease. Extended disease SCLC (ED-SCLC) patients with synaptophysin expression had a higher response to chemotherapy compared to those without staining (p = 0.01); on the other hand, the chemotherapy response of these patients was not significantly different when they expressed CK7 (p = 0.06). Pancytokeratin expression was associated with favorable survival in both limited disease SCLC (LD-SCLC) (p = 0.02) and ED-SCLC (p = 0.005) patients. Similarly, ED-SCLC patients with CD56 staining lived longer than those without expression (p = 0.001). The lack of synaptophysin expression in LD-SCLC patients (p = 0.06) and TTF-1 expression in ED-SCLC patients (p = 0.06) were correlated with better survival rates. CONCLUSION: We conclude that IHC markers, used frequently in the diagnosis of SCLC, might also be used in clinical decision-making, since they are correlated with predictive and prognostic factors for the disease.

Expression of CK7 and CDKN2 in Cervical Intraepithelial Neoplasia and Correlation with Clinical Outcome.

AIM: To evaluate cyclin-dependent kinase inhibitor 2A (CDKN2A) and cytokeratin 7 (CK7) expression in cervical intraepithelial neoplasia (CIN) formalin-fixed samples. MATERIALS AND METHODS: Staining with antibody clones G175-405 for CDKN2A and OV-TL 12/30 for CK7 were evaluated and the detection of protein expressions were compared in 147 patients with CIN. RESULTS: Clinical follow-up of patients with CIN1 and CIN2 showed that most patients had a favorable outcome. Single CDKN2A or CK7 expression and their combined expression had a greater sensitivity and negative predictive value in CIN1, corresponding to the non-development of the disease. The positive predictive value of CDKN2A was greater than that of CK7. Combined expression of CDKN2A and CK7 showed that the sensitivity, specificity, positive predictive values, and negative predictive values had their maximum index in the CIN1 group. Analysis of combined expression of CDKN2A and CK7 showed that 85.7% of patients presented unfavorable clinical outcomes, with positive expression for both markers identified in CIN2. CONCLUSION: Combined expression of CK7 and CDKN2A was associated with a better diagnosis of CIN, and negative expression in CIN1/2 groups had a greater negative predictive value for patient clinical outcome.

BRAF-mutated microsatellite stable colorectal carcinoma: an aggressive adenocarcinoma with reduced CDX2 and increased cytokeratin 7 immunohistochemical expression.

Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal carcinoma with BRAF mutation and high-level microsatellite instability (MSI-H) has been well documented. The immunophenotype of BRAF-mutated microsatellite stable (MSS) colorectal carcinoma has not been reported. We analyzed 205 colorectal carcinomas including 28 BRAF-mutated MSS, 53 BRAF-mutated MSI-H, and 124 BRAF wild-type MSS tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression. CDX2 was scored semiquantitatively for both staining intensity and percent of tumor cells staining and a modified CDX2 H-score was calculated. Patients with BRAF-mutated MSS colorectal carcinomas were more frequently stage IV at presentation compared to patients with BRAF-mutated MSI-H colorectal carcinomas and BRAF wild-type MSS colorectal carcinomas (32% versus 8% versus 15%, P < .001). BRAF-mutated MSS colorectal carcinoma displayed reduced CDX2 expression compared to BRAF wild-type MSS colorectal carcinoma (75% versus 94%; mean CDX2 H-score 98 versus 150, P < .001). CK7 expression was more often identified in BRAF-mutated MSS colorectal carcinoma compared to both BRAF-mutated MSI-H colorectal carcinoma and BRAF wild-type MSS colorectal carcinoma (39% versus 6% versus 6%, P = .0001). BRAF-mutated MSI-H colorectal carcinomas were less often CK20 positive compared to BRAF-mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus 90%, P = 0.001). In summary, BRAF-mutated MSS colorectal carcinoma often displays reduced CDX2 and increased CK7 expression. Knowledge of this altered immunophenotype is important as patients with BRAF-mutated MSS colorectal carcinoma often present with metastatic disease and the altered tumor immunophenotype may lead to the erroneous assumption that origin from the colon/rectum is unlikely.

Pure micropapillary rectal carcinoma with CK7 and CK20 coexpression and loss of CDX2 reactivity / Carcinoma micropapilar rectal puro con coexpresión de CK7 y CK20 y pérdida de reactividad CDX2

The micropapillary carcinoma is regarded as an aggressive variant of adenocarcinoma in any location. Histologically is characterized by papillary cell clusters surrounded by clear spaces. The reported proportion of micropapillary carcinoma component to the entire tumor ranged from 5 to 80 percent and no pure cases has been reported. There are near of 130 cases reported to date in colorectum. We experienced a patient with a pure micropapillary carcinoma showing coexpression of CK7, CK20, and absence of CDX2, which had an aggressive neoplasm with extense perineural, vascular and lymphatic invasion also extensive nodal metastasis. The presence of a micropapillary carcinoma in the colorectum seemed to be closely related with nodal metastasis, similar to the case for micropapillary carcinomas in other organs. Therefore, if a micropapillary component is identified in a tumor, particularly in a biopsy specimen, even if the pre-operative diagnosis is a pedunculated early colorectal cancer, should be carefully consider the extent of surgical resection due to the high potential for nodal metastasis.

El carcinoma micropapilar es considerado como una variante agresiva del cáncer en cualquier localización. Histológicamente se caracteriza por grupos de células papilares rodeada de espacios libres. Se informó que la proporción del componente carcinoma micropapilar en la totalidad de un tumor varió entre 5 por ciento a 80 por ciento y no se han reportado casos puros. Existen cerca de 130 casos reportados hasta la fecha en colon y recto. Se describe el caso de un paciente con un carcinoma micropapilar puro que muestra coexpresión de CK7, CK20, y la ausencia de CDX2, que tenía un tumor agresivo con extensa invasión perineural, vascular y linfática además de metástasis nodular extensa. La presencia de un carcinoma micropapilar en la región colorrectal parece estar estrechamente relacionada con metástasis nodular, similar al caso del carcinomas micropapilar en otros órganos. Por lo tanto, si un componente micropapilar se identifica en un tumor, sobre todo en una muestra de biopsia, incluso si el diagnóstico pre-operatorio es un cáncer colorrectal temprano pediculado, se debe considerar cuidadosamente la extensión de la resección quirúrgica debido a la alta probabilidad de metástasis nodular.

Apocrine Adenocarcinoma in the Eyelid of a Miniature Pinscher

A 12-year-old spayed female miniature pinscher canid presented to the referring veterinarian with a 1 month history of a right eyelid mass. No other masses besides a previously diagnosed lipoma were identified after physical examination and thoracic radiographic examination. Histologically, neoplastic cells formed glands and were subdivided by a fibrous stroma, exhibited moderate cellular pleomorphism, and were immunoreactive for cytokeratin 7. Based on these findings an apocrine adenocarcinoma of the eyelid was diagnosed.(AU)

Apocrine adenocarcinoma in the eyelid of a miniature pinscher

A 12-year-old spayed female miniature pinscher canid presented to the referring veterinarian with a 1 month history of a right eyelid mass. No other masses besides a previously diagnosed lipoma were identified after physical examination and thoracic radiographic examination. Histologically, neoplastic cells formed glands and were subdivided by a fibrous stroma, exhibited moderate cellular pleomorphism, and were immunoreactive for cytokeratin 7. Based on these findings an apocrine adenocarcinoma of the eyelid was diagnosed.