New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome.

We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphovascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.8 months. Seventy-three patients (21%) had pattern A tumors; all were stage I and there were no LN metastases or recurrences. Pattern B was seen in 90 tumors (26%); all were stage I and LVI was seen in 24 cases (26.6%). Nodal disease was found in only 4 (4.4%) pattern B tumors (one IA2, two IB1, one IB not further specified (NOS)), each of which showed LVI. Pattern C was found in 189 cases (54%), 117 had LVI (61.9%) and 17% were stage II or greater. Forty-five (23.8%) patients showed LN metastases (one IA1, 14 IB1, 5 IB2, 5 IB NOS, 11 II, 5 III and 4 IV) and recurrences were recorded in 41 (21.7%) patients. This new risk stratification system identifies a subset of stage I patients with essentially no risk of nodal disease, suggesting that patients with pattern A tumors can be spared lymphadenectomy. Patients with pattern B tumors rarely present with LN metastases, and sentinel LN examination could potentially identify these patients. Surgical treatment with nodal resection is justified in patients with pattern C tumors.

Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.

The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.

Invasive endocervical adenocarcinoma: a new pattern-based classification system with important clinical significance.

A new 3-tier pattern-based system to classify endocervical adenocarcinoma was recently presented. In short, pattern A tumors were characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture. Pattern B tumors demonstrated localized destructive invasion defined as desmoplastic stroma surrounding glands with irregular and/or ill-defined borders or incomplete glands and associated tumor cells (individual or small clusters) within the stroma. Tumors with pattern C showed diffusely infiltrative glands with associated extensive desmoplastic response. In total, 352 cases (all FIGO stages) from 12 institutions were identified. Mean patient age was 45 years (range, 20 to 83 y). Forty-nine (13.9%) cases demonstrated lymph nodes (LNs) with metastatic endocervical carcinoma. Using this new system, 73 patients (20.7%) were identified with pattern A tumors (all stage I); none had LN metastases and/or recurrences. Ninety patients (25.6%) were identified with pattern B tumors (all stage I); only 4 (4.4%) had LN metastases; 1 had vaginal recurrence. The 189 (53.7%) remaining patients had pattern C tumors; 45 (23.8%) of them had LN metastases. This new classification system demonstrated 20.7% of patients (pattern A) with negative LNs, and patients with pattern A tumors can be spared of lymphadenectomy. Patients with pattern B tumors rarely presented with metastatic LNs, and sentinel LN examination could potentially identify these patients. Aggressive treatment is justified in patients with pattern C tumors.

Pim-2 upregulation: biological implications associated with disease progression and perinueral invasion in prostate cancer.

BACKGROUND: The serine/threonine kinase Pim-2 acts as a transcriptionally regulated apoptotic inhibitor and is implicated in prosurvival. Pim-2 has been implicated in many apoptotic pathways. MATERIALS AND METHODS: Silencer validated short interfering RNA (siRNA) to Pim-2, Silencer GAPDH siRNA, and one scrambled siRNA for eliciting RNAi were transfected separately into DU-145/DRG in vitro model. Total RNA was extracted, purified, and validated by Quantitative RT-PCR 48 hr after transfection. The effects of Pim-2 silencing in vitro were evaluated by Western blot and immunofluroscence and collaborated with Ki-67 and TUNEL. The first microarrays (0.6 mm) had 640 radical prostatectomies while the second array (2 mm) used 226 perineural invasion (PNI) cases. RESULTS: mRNA level of Pim-2 in experimental samples was 99% decreased. The experimental samples (mean 7.6 +/- 0.52%) had significantly higher apoptosis than controls (mean 0.89 +/- 0.014%) (P = 0.000). Conversely, proliferation (Ki-67 index) of the experimental samples (mean 57.1 +/- 3.94%) was lower than controls(mean 64.7 +/- 3.1%), but not significant (P = 0.0979). Both nuclear and cytoplasmic Pim-2 were increased in PNI than in prostate cancer (PCa) away from the nerve. Increased nuclear Pim-2 in PCa was associated with many established prognostic factors. Increased Pim-2 levels (nuclear or cytoplasmic) also correlated with NFkappaB nuclear translocation, higher proliferation, and reduced apoptosis. Higher level of nuclear Pim-2 in the PCa was associated with higher risk of biochemical recurrence (HR: 1.021-2.419, P = 0.0399). CONCLUSION: Pim-2 is an important prosurvival gene, which might result in activation of enhanced anti-apoptotic pathway, leading to a more aggressive phenotype of PCa. Pim-2 may become a target for novel therapeutic strategies.